Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells.
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.
Good
Kim L
KL
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Avery
Danielle T
DT
Tangye
Stuart G
SG
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory / Q000235:genetics; D005810:Multigene Family / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7