Antigen-specific B cell memory: expression and replenishment of a novel b220(-) memory b cell compartment.
The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220(-)CD138(-)) that are distinct from antibody-secreting B cells (B220(+/)-CD138(+)) and B220(+)CD138(-) memory B cells. These nonsecreting somatically mutated B220(-) memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75-85%) and the bone marrow (>95%) expresses the B220(-) phenotype. Upon adoptive transfer, B220(-) memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220(+) counterparts. The pattern of cellular differentiation after transfer indicates that B220(-) memory B cells act as stable self-replenishing intermediates that arise from B220(+) memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220(-) compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.
McHeyzer-Williams
L J
LJ
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cool
M
M
McHeyzer-Williams
M G
MG
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology; D051925:CD79 Antigens; D002454:Cell Differentiation; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D053668:Syndecan-1; D053667:Syndecans
C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D015703:Antigens, CD; D051925:CD79 Antigens; C497884:Cd79b protein, mouse; D006241:Haptens; D007146:Immunoglobulin lambda-Chains; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D006433:Hemocyanins; D017493:Leukocyte Common Antigens