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* Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia;
Faculty of Medicine, University of Sydney, New South Wales, Australia; and
Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of naive and memory B cells that result in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM (signaling lymphocytic activation molecule), B7, and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation, and Ig secretion, and they entered division more rapidly than did naive B cells in response to both T cell-dependent and T cell-independent stimuli. Furthermore, both IgM and isotype-switched memory B cells, but not naive B cells, costimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that up-regulation of genes involved in activation, costimulation, and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool.
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 This work was supported by the National Health and Medical Research Council (NHMRC) of Australia and the Cancer Institute, New South Wales (NSW). K.L.G. was the recipient of postgraduate Research Awards from the University of Sydney and a Cancer Institute NSW Research Scholar Award. S.G.T. is the recipient of a Senior Research Fellowship awarded by the NHMRC of Australia.
2 Current address: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510.
3 Address correspondence and reprint requests to Dr. Stuart Tangye, Immunology and Inflammation Department, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst 2010, New South Wales, Australia. E-mail address: s.tangye{at}garvan.org.au
4 Abbreviations used in this paper: ISC, Ig-secreting cell; APRIL, a proliferation-inducing ligand; BAFF, B cell-activating factor of the TNF family; BCMA, B cell maturation Ag; CRACC, CD2-like receptor-activating cytotoxic cells; GC, germinal center; MNC, mononuclear cell; PB, peripheral blood; PC, plasma cell; PD, programmed death; SA, streptavidin; SLAM, signaling lymphocytic activation molecule; TACI, transmembrane activator and calcium modulator ligand interactor; TNFSF, TNF superfamily; TNFRSF, TNF receptor superfamily; ttfd, time to first division.
5 The online version of this article contains supplemental material.
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