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Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
Memory B cells are generated in germinal centers (GC) and contribute to serological immunity by rapidly differentiating into plasma cells. Human memory B cells can be identified by the expression of CD27. These cells exhibit more rapid responses than naive (CD27–) B cells following stimulation in vitro, consistent with the heightened kinetics of secondary responses in vivo. CD27+ B cells express mutated Ig V region genes; however a significant proportion continue to express IgM, suggesting the existence of IgM+ memory B cells. The observation that mutated IgM+CD27+ B cells are generated in humans who cannot form GC led to the conclusions that these cells are generated independently of GC and thus are not memory cells and that they mediate responses to T cell-independent Ag. Although some studies support the idea that IgM+CD27+ B cells participate in T cell-independent responses, many others do not. In this review we will provide alternate interpretations of the biology of IgM+CD27+ B cells and propose that they are indeed memory cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Work performed in the Tangye laboratory is supported by the National Health and Medical Research Council (NHMRC) of Australia. K.L.G was the recipient of a Postgraduate Research Award from the University of Sydney and a Cancer Institute New South Wales Research Scholar Award. S.G.T. is the recipient of an R. D. Wright Career Development Award from the NHMRC of Australia.
2 Address correspondence and reprint requests to Dr. Stuart Tangye, Immunology and Inflammation Department, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail address: s.tangye{at}garvan.org.au
3 Current address: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510
4 Abbreviations used in this paper: GC, germinal center; AID, activation-induced cytidine deaminase; CVID, common variable immunodeficiency; HIGM, hyper-IgM; MZ, marginal zone; PB, peripheral blood; SHM, somatic hypermutation; TD, T dependent; TI, T independent; XLP, X-linked lymphoproliferative disease.
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