Development and maintenance of a B220- memory B cell compartment.
We have recently demonstrated that a novel somatically mutated B220(-) memory B cell subset rapidly dominates the secondary immune response to (4-hydroxy-3-nitrophenyl) acetyl (NP). Upon adoptive transfer with Ag, B220(+)NP(+) memory B cells produce large numbers of B220(-)NP(+) B cells that can rapidly differentiate into plasma cells. Therefore, it is not clear whether the novel B220(-) memory compartment is a consequence of secondary Ag challenge or whether it develops as a stable memory subset after initial Ag challenge. In this study, we demonstrate the gradual emergence of B220(-)NP(+) B cells in the spleen to maximal numbers 3 wk after initial Ag exposure. Like their B220(+) counterparts, the B220(-) B cells initially appear unmutated at days 5-7; however, the majority rapidly accumulate affinity increasing mutations by days 9-14 of the primary immune response. More extensive cell surface phenotype (GL7(-)BLA-1(-)CD24(-)CD43(+)) argues strongly against germinal center localization and direct analysis in situ places a cohort of B220(-)CD11b(+)NP(+) B cells in the red pulp of the spleen and not in the MZs. These data provide direct evidence for the development of B220(-) memory B cells as a unique cellular consequence of primary Ag exposure. The cellular dynamics and molecular attributes of these unique memory B cells suggest they are distinct cellular products of the germinal center reaction in the primary response and are maintained long-term in the spleen and bone marrow.
Driver
D J
DJ
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
McHeyzer-Williams
L J
LJ
Cool
M
M
Stetson
D B
DB
McHeyzer-Williams
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D013154:Spleen / Q000166:cytology / Q000276:immunology
D018985:Epitopes, B-Lymphocyte; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007146:Immunoglobulin lambda-Chains; D016177:Macrophage-1 Antigen; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D007073:Immunoglobulin E; D017493:Leukocyte Common Antigens