A checkpoint for autoreactivity in human IgM+ memory B cell development.
Autoantibodies are removed from the repertoire at two checkpoints during B cell development in the bone marrow and the periphery. Despite these checkpoints, up to 20% of the antibodies expressed by mature naive B cells in healthy humans show low levels of self-reactivity. To determine whether self-reactive antibodies are also part of the antigen-experienced memory B cell compartment, we analyzed recombinant antibodies cloned from single circulating human IgM+ memory B cells. Cells expressing antibodies specific for individual bacterial polysaccharides were expanded in the IgM+ memory compartment. In contrast, B cells expressing self-reactive and broadly bacterially reactive antibodies were removed from the repertoire in the transition from naive to IgM+ memory B cell. Selection against self-reactive antibodies was implemented before the onset of somatic hypermutation. We conclude that a third checkpoint selects against self-reactivity during IgM+ memory B cell development in humans.
Tsuiji
Makoto
M
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Yurasov
Sergey
S
Velinzon
Klara
K
Thomas
Saskia
S
Nussenzweig
Michel C
MC
Wardemann
Hedda
H
D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007156:Immunologic Memory; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013205:Staphylococcal Protein A / Q000276:immunology
D000942:Antigens, Bacterial; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D011135:Polysaccharides, Bacterial; D013205:Staphylococcal Protein A; C119204:streptococcal protective antigen