{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:35:12Z","timestamp":1787877312296,"version":"build-2784847793"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Principal Research Fellowship"},{"name":"Postdoctoral Fellowship"},{"name":"Research Foundation-Flanders (FWO), Belgium"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>Immunological memory is characterized by the rapid reactivation of memory B cells that produce large quantities of high\u2010affinity antigen\u2010specific antibodies. This contrasts the response of na\u00efve B cells, and the primary immune response, which is much slower and of lower affinity. Memory responses are critical for protection against infectious diseases and form the basis of most currently available vaccines. Although we have known about the phenomenon of long\u2010lived memory for centuries, the biochemical differences underlying these diverse responses of na\u00efve and memory B cells is incompletely resolved. Here we investigated the nature of B\u2010cell receptor (BCR) signaling in human splenic na\u00efve, IgM<jats:sup>+<\/jats:sup> memory and isotype\u2010switched memory B cells following multivalent BCR crosslinking. We observed comparable rapid and transient phosphorylation kinetics for proximal (phosphotyrosine and spleen tyrosine kinase) and propagation (B\u2010cell linker, phospholipase C\u03b32) signaling components in these different B\u2010cell subsets. However, the magnitude of activation of downstream components of the BCR signaling pathway were greater in memory compared with na\u00efve cells. Although no differences were observed in the magnitude of Ca<jats:sup>2+<\/jats:sup> mobilization between subsets, IgM<jats:sup>+<\/jats:sup> memory B cells exhibited a more rapid Ca<jats:sup>2+<\/jats:sup> mobilization and a greater depletion of the Ca<jats:sup>2+<\/jats:sup> endoplasmic reticulum stores, while IgG<jats:sup>+<\/jats:sup> memory B cells had a prolonged Ca<jats:sup>2+<\/jats:sup> uptake. Collectively, our findings show that intrinsic signaling features of B\u2010cell subsets contribute to the robust response of human memory B cells over na\u00efve B cells. This has implications for our understanding of memory B\u2010cell responses and provides a framework to modulate these responses in the setting of vaccination and immunopathologies, such as immunodeficiency and autoimmunity.<\/jats:p>","DOI":"10.1038\/icb.2016.41","type":"journal-article","created":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T08:28:35Z","timestamp":1461313715000},"page":"774-786","source":"Crossref","is-referenced-by-count":28,"title":["Na\u00efve and memory B cells exhibit distinct biochemical responses following BCR engagement"],"prefix":"10.1111","volume":"94","author":[{"given":"Leen","family":"Moens","sequence":"first","affiliation":[{"name":"Immunology Division, Garvan Institute of Medical Research  Darlinghurst New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Kane","sequence":"additional","affiliation":[{"name":"Immunology Division, Garvan Institute of Medical Research  Darlinghurst New South 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