{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:33:23Z","timestamp":1791282803490,"version":"4.1.0"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,9,15]]},"abstract":"<jats:p>Isolation of large numbers of surface IgD+CD38\u2212 naive and surface IgD\u2212CD38\u2212 memory B cells allowed us to study the intrinsic differences between these two populations. Upon in vitro culture with IL-2 and IL-10, human CD40\u2013activated memory B cells undergo terminal differentiation into plasma cells more readily than do naive B cells, as they give rise to five- to eightfold more plasma cells and three- to fourfold more secreted immunoglobulins. By contrast, naive B cells give rise to a larger number of nondifferentiated B blasts. Saturating concentrations of CD40 ligand, which fully inhibit naive B cell differentiation, only partially affect that of memory B cells. The propensity of memory B cells to undergo terminal plasma cell differentiation may explain the extensive extra follicular plasma cell reaction and the limited germinal center reaction observed in vivo after secondary immunizations, which contrast with primary responses in carrier-primed animals. This unique feature of memory B cells may confer two important capacities to the immune system: (a) the rapid generation of a large number of effector cells to efficiently eliminate the pathogens; and (b) the prevention of the overexpansion and chronic accumulation of one particular memory B cell clone that would freeze the available peripheral repertoire.<\/jats:p>","DOI":"10.1084\/jem.186.6.931","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"931-940","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["Memory B Cells Are Biased Towards Terminal Differentiation: A Strategy That May Prevent Repertoire Freezing"],"prefix":"10.1084","volume":"186","author":[{"given":"Christophe","family":"Arpin","sequence":"first","affiliation":[{"name":"From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Banchereau","sequence":"additional","affiliation":[{"name":"From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,9,15]]},"reference":[{"key":"2023072507422657600_B1"},{"key":"2023072507422657600_B2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0167-5699(92)90199-H","article-title":"Germinal centers in T-cell\u2013dependent antibody responses","volume":"13","author":"Liu","year":"1992","journal-title":"Immunol Today"},{"key":"2023072507422657600_B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0092-8674(92)90198-L","article-title":"The molecular and cellular basis of affinity maturation in the antibody response","volume":"68","author":"Nossal","year":"1992","journal-title":"Cell"},{"key":"2023072507422657600_B4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev.iy.11.040193.000405","article-title":"Immunological memory","volume":"11","author":"Gray","year":"1993","journal-title":"Annu Rev Immunol"},{"key":"2023072507422657600_B5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1146\/annurev.iy.12.040194.001001","article-title":"Germinal centers","volume":"12","author":"MacLennan","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2023072507422657600_B6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0092-8674(94)90329-8","article-title":"Developmental switches in the immune system","volume":"76","author":"Weissman","year":"1994","journal-title":"Cell"},{"key":"2023072507422657600_B7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0065-2776(08)60587-8","article-title":"In situ studies of the germinal center reaction","volume":"60","author":"Kelsoe","year":"1995","journal-title":"Adv Immunol"},{"key":"2023072507422657600_B8","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1096\/fasebj.8.11.8070632","article-title":"Biology of germinal centers in lymphoid tissue","volume":"8","author":"Thorbecke","year":"1994","journal-title":"FASEB J"},{"key":"2023072507422657600_B9","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/0167-5699(85)90024-6","article-title":"The molecular evolution of the immune response","volume":"6","author":"Manser","year":"1985","journal-title":"Immunol Today"},{"key":"2023072507422657600_B10","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/0092-8674(91)90289-B","article-title":"Maturation of the immune response in germinal centers","volume":"67","author":"Berek","year":"1991","journal-title":"Cell"},{"key":"2023072507422657600_B11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/354389a0","article-title":"Intraclonal generation of antibody mutants in germinal centres","volume":"354","author":"Jacob","year":"1991","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B12","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1002\/j.1460-2075.1993.tb06189.x","article-title":"Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections","volume":"12","author":"K\u00fcppers","year":"1993","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072507422657600_B13","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1084\/jem.178.1.295","article-title":"Antigen-driven B cell differentiation in vivo","volume":"178","author":"McHeyzer-Williams","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507422657600_B14","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1084\/jem.180.4.1383","article-title":"Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age","volume":"180","author":"Klein","year":"1994","journal-title":"J Exp Med"},{"key":"2023072507422657600_B15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1084\/jem.180.1.329","article-title":"Analysis of somatic mutation in five B cell subsets of human tonsil","volume":"180","author":"Pascual","year":"1994","journal-title":"J Exp Med"},{"key":"2023072507422657600_B16","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/381751a0","article-title":"Clonal selection and learning in the antibody system","volume":"381","author":"Rajewsky","year":"1996","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B17","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/298377a0","article-title":"Germinal centre B cells: antigen specificity and charges in heavy chain class expression","volume":"298","author":"Kraal","year":"1982","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B18","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1074-7613(00)80432-X","article-title":"Within germinal centers isotype switching of immunoglobulin genes occurs after onset of somatic mutation","volume":"4","author":"Liu","year":"1996","journal-title":"Immunity"},{"key":"2023072507422657600_B19","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1084\/jem.183.5.2303","article-title":"Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation","volume":"183","author":"Toellner","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507422657600_B20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/eji.1830180306","article-title":"Memory B cells in T cell\u2013dependent antibody responses colonize the splenic marginal zones","volume":"18","author":"Liu","year":"1988","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1600-065X.1986.tb01484.x","article-title":"Antigen-driven selection of virgin and memory B cells","volume":"91","author":"MacLennan","year":"1986","journal-title":"Immunol Rev"},{"key":"2023072507422657600_B22"},{"key":"2023072507422657600_B23","first-page":"V","article-title":"Immunological memory","volume":"159","author":"Gray","year":"1990","journal-title":"Curr Top Microbiol Immunol"},{"key":"2023072507422657600_B24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.iy.09.040191.001205","article-title":"Memory B and T cells","volume":"9","author":"Vitetta","year":"1991","journal-title":"Annu Rev Immunol"},{"key":"2023072507422657600_B25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0065-2776(08)60501-5","article-title":"Immunological memory","volume":"53","author":"Mackay","year":"1993","journal-title":"Adv Immunol"},{"key":"2023072507422657600_B26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0092-8674(94)90338-7","article-title":"T and B memory cells","volume":"76","author":"Sprent","year":"1994","journal-title":"Cell"},{"key":"2023072507422657600_B27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.272.5258.54","article-title":"Immunological memory and protective immunity: understanding their relation","volume":"272","author":"Ahmed","year":"1996","journal-title":"Science (Wash DC)"},{"key":"2023072507422657600_B28","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/373441a0","article-title":"Cell-autonomous Fas (CD95)\/ Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas","volume":"373","author":"Brunner","year":"1995","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B29","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/373438a0","article-title":"Autocrine T-cell suicide mediated by APO-1(Fas\/CD95)","volume":"373","author":"Dhein","year":"1995","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/373444a0","article-title":"Fas (CD95)\/FasL interactions required for programmed cell death after T-cell activation","volume":"373","author":"Ju","year":"1995","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B31","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1084\/jem.182.5.1265","article-title":"Fas ligation induces apoptosis of CD40-activated human B lymphocytes","volume":"182","author":"Garrone","year":"1995","journal-title":"J Exp Med"},{"key":"2023072507422657600_B32","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/intimm\/5.10.1259","article-title":"Phenotypic and functional heterogeneity of the IgD\u2212B cell compartment: identification of two major tonsillar B cell subsets","volume":"5","author":"Lagresle","year":"1993","journal-title":"Int Immunol"},{"key":"2023072507422657600_B33","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/1074-7613(95)90048-9","article-title":"Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid upregulation of B7.1 and B7.2","volume":"2","author":"Liu","year":"1995","journal-title":"Immunity"},{"key":"2023072507422657600_B34","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/intimm\/8.5.737","article-title":"Centrocytes rapidly adopt a memory B cell phenotype on co-culture with autologous germinal centre T cell\u2013enriched preparations","volume":"8","author":"Casamayor-Palleja","year":"1996","journal-title":"Int Immunol"},{"key":"2023072507422657600_B35","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1073\/pnas.91.4.1323","article-title":"Switch recombination in normal IgA1+B lymphocytes","volume":"91","author":"Irsch","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507422657600_B36","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1182\/blood.V89.4.1288","article-title":"Evidence for a large compartment of IgM-expressing memory B cells in humans","volume":"89","author":"Klein","year":"1997","journal-title":"Blood"},{"key":"2023072507422657600_B37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1126\/science.7537388","article-title":"Generation of memory B cells and plasma cells in vitro","volume":"268","author":"Arpin","year":"1995","journal-title":"Science (Wash DC)"},{"key":"2023072507422657600_B38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1084\/jem.135.2.277","article-title":"Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to \u03bc-chain","volume":"135","author":"Lawton","year":"1972","journal-title":"J Exp Med"},{"key":"2023072507422657600_B39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0923-2494(91)90069-U","article-title":"The initiation of germinal centre reactivity","volume":"142","author":"Kroese","year":"1991","journal-title":"Res Immunol"},{"key":"2023072507422657600_B40","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1002\/eji.1830211209","article-title":"Sites of specific B cell activation in primary and secondary responses to T cell\u2013dependent and T cell\u2013independent antigens","volume":"21","author":"Liu","year":"1991","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B41","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0923-2494(91)90063-O","article-title":"Are Peyer's patch germinal centre reactions different from those occuring in other lymphoid tissues?","volume":"142","author":"Cebra","year":"1991","journal-title":"Res Immunol"},{"key":"2023072507422657600_B42","first-page":"1","article-title":"The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation","volume":"46","author":"Benner","year":"1981","journal-title":"Clin Exp Immunol"},{"key":"2023072507422657600_B43","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/eji.1830161018","article-title":"Distinct short-lived and long-lived antibody-producing cell populations","volume":"16","author":"Ho","year":"1986","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1084\/jem.183.1.227","article-title":"Bcl-2 positive tonsillar plasma cells are rescued from prompt apoptosis by bone marrow fibroblasts","volume":"183","author":"Merville","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507422657600_B45","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/0092-8674(90)90420-J","article-title":"Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity","volume":"63","author":"Webb","year":"1990","journal-title":"Cell"},{"key":"2023072507422657600_B46","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1126\/science.1900951","article-title":"Peripheral selection of the T cell repertoire","volume":"251","author":"Rocha","year":"1991","journal-title":"Science (Wash DC)"},{"key":"2023072507422657600_B47","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/362758a0","article-title":"Virus persistence in acutely immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells (erratum published 364:262)","volume":"362","author":"Moskophidis","year":"1993","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B48","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1600-065X.1993.tb01535.x","article-title":"Factors controlling the reactivity of immature and mature T cells to Mls antigens in vivo","volume":"131","author":"Webb","year":"1993","journal-title":"Immunol Rev"},{"key":"2023072507422657600_B49","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/intimm\/7.11.1809","article-title":"CD40 cross-linking inhibits specific antibody production by human B cells","volume":"7","author":"Callard","year":"1995","journal-title":"Int Immunol"},{"key":"2023072507422657600_B50","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1002\/eji.1830250646","article-title":"CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation","volume":"25","author":"Lane","year":"1995","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B51","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S1074-7613(00)80408-2","article-title":"CD40 and its ligand in host defense","volume":"4","author":"Noelle","year":"1996","journal-title":"Immunity"},{"key":"2023072507422657600_B52","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.4049\/jimmunol.149.12.3817","article-title":"Molecular interactions mediating T\u2013B lymphocyte collaboration in human lymphoid follicles. Roles of T cell\u2013B cell\u2013activating molecule (5c8 antigen) and CD40 in contact-dependent help","volume":"149","author":"Lederman","year":"1992","journal-title":"J Immunol"},{"key":"2023072507422657600_B53","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1084\/jem.178.5.1555","article-title":"In vivo CD40\u2013gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T\u2013B cell interactions","volume":"178","author":"van den Eetwegh","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507422657600_B54","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1084\/jem.181.4.1293","article-title":"A subset of CD4+memory T cells contains preformed CD40 ligand that is rapidly but transiently expressed on their surface after activation through the T cell receptor complex","volume":"181","author":"Casamayor-Palleja","year":"1995","journal-title":"J Exp Med"},{"key":"2023072507422657600_B55","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/342929a0","article-title":"Mechanisms of antigen-driven selection in germinal centers","volume":"342","author":"Liu","year":"1989","journal-title":"Nature (Lond)"},{"key":"2023072507422657600_B56","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1002\/eji.1830230948","article-title":"Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bcl-2 induction","volume":"23","author":"Holder","year":"1993","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B57","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1600-065X.1996.tb00695.x","article-title":"B\u2013T lymphocyte interactions in the generation and survival of memory cells","volume":"150","author":"Gray","year":"1996","journal-title":"Immunol Rev"},{"key":"2023072507422657600_B58","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1073\/pnas.83.12.4494","article-title":"Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50","volume":"83","author":"Clark","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507422657600_B59","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/eji.1830171026","article-title":"Synergistic interaction between interleukin 4 and anti-Bp50 (CDw40) revealed in a novel B cell restimulation assay","volume":"17","author":"Gordon","year":"1987","journal-title":"Eur J Immunol"},{"key":"2023072507422657600_B60","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1084\/jem.176.6.1543","article-title":"Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion","volume":"176","author":"Spriggs","year":"1992","journal-title":"J Exp Med"},{"key":"2023072507422657600_B61","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1146\/annurev.iy.12.040194.004313","article-title":"The CD40 antigen and its Ligand","volume":"12","author":"Banchereau","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2023072507422657600_B62","doi-asserted-by":"crossref","first-page":"17478","DOI":"10.1016\/S0021-9258(19)47397-3","article-title":"Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover, and multiple previously unidentified serine\/threonine-specific protein kinases by the pan\u2013B-cell receptor CD40\/ Bp50 at discrete developmental stages of human B-cell ontogeny","volume":"266","author":"Uckun","year":"1991","journal-title":"J Biol Chem"},{"key":"2023072507422657600_B63","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1002\/eji.1830231030","article-title":"Protein tyrosine phosphorylation is mandatory for CD40-mediated rescue of germinal center B cells from apoptosis","volume":"23","author":"Knox","year":"1993","journal-title":"Eur J Immunol"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/6\/931\/1686264\/96-2262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/6\/931\/1686264\/96-2262.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T08:27:56Z","timestamp":1690273676000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/186\/6\/931\/7289\/Memory-B-Cells-Are-Biased-Towards-Terminal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,9,15]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1997,9,15]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.186.6.931","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,9,15]]}}}