{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:20:23Z","timestamp":1761708023760},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":6895,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1987,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>C57BL\/6 mice were chronically treated with milligram doses of the noncytotoxic monoclonal anti\u2010\u03bc<jats:sup>b<\/jats:sup> antibody MB86 (IgG<jats:sub>1<\/jats:sub>,<jats:italic>x<\/jats:italic>) from birth or from fetal life. The spleens of the manipulated animals contained large numbers (25% as compared to control mice) of B lineage cells which expressed IgM<jats:sup>b<\/jats:sup> on the surface after overnight incubation <jats:italic>in vitro<\/jats:italic>. The spleens also contained B cells whose surface IgM was unreactive with antibody MB86. A few such cells were immortalized by cell fusion. They included cells secreting \u03bc together with \u03bb<jats:sub>2<\/jats:sub> chains which apparently prevent recognition by antibody MB86, and a point mutant in the first constant domain of the \u03bc chain, changing the <jats:italic>b<\/jats:italic> to the <jats:italic>a<\/jats:italic> allotype. Cells expressing MB86<jats:sup>\u2212<\/jats:sup> surface IgM did not selectively expand under MB86 treatment over the first few months of life.<\/jats:p><jats:p>Serum Ig levels in the manipulated mice were normal except for IgM which was undetectable in most instances. In some animals low levels of MB86<jats:sup>\u2212<\/jats:sup> IgM molecules were produced. At 7 weeks of age, mice treated with MB86 from birth produced normal\u2010size IgG anti\u2010(4\u2010hydroxy\u20103\u2010nitrophenyl)acetyl (NP) responses with the usual predominance of \u03bb<jats:sub>1<\/jats:sub> chain\u2010bearing IgG<jats:sub>1<\/jats:sub> antibodies. At the age of 5\u20136 months, and also in young mice treated with MB86 from fetal life, the responses were variable and presumably oligoclonal, with a tendency towards the production of antibodies with \u03b3<jats:sub>3<\/jats:sub> heavy and \u03bb<jats:sub>2<\/jats:sub> or \u03bb<jats:sub>3<\/jats:sub> light chains. We interpret these results to mean that B cells hit by antibody MB86 from the time of their generation become unresponsive to T cell\u2010dependent stimulation, but are still able to expand. Occasionally, they escape functional suppression through class switching (to IgG<jats:sub>3<\/jats:sub>) upon mitogenic stimulation. At birth, C57BL\/6 mice contain a mature B cell population which mediates normal immune responses under MB86 treatment and eventually dies out.<\/jats:p><jats:p>Taken as a model of tolerance induction in B cells, the data provide evidence for \u201ctolerant\u201d cells and support the concept of an early phase of sensitivity to tolerance induction in B cell differentiation.<\/jats:p><jats:p>The anti\u2010NP response under MB86 treatment differed profoundly from control responses in idiotypic terms, but became normal as the animals recovered from suppression. This may reflect blockade by MB86 of idiotypic selection within the B cell population.<\/jats:p>","DOI":"10.1002\/eji.1830170714","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:37:21Z","timestamp":1172709441000},"page":"981-990","source":"Crossref","is-referenced-by-count":17,"title":["<i>In vivo<\/i> generation and function of B cells in the presence of a monoclonal anti\u2010IgM antibody: implications for B cell tolerance"],"prefix":"10.1002","volume":"17","author":[{"given":"Angela","family":"Gause","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuaki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Kappen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1980.tb00329.x"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-3045-5_8"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4049\/jimmunol.113.1.120","volume":"113","author":"Martin L. 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