Differential regulation of self-reactivity discriminates between IgG+ human circulating memory B cells and bone marrow plasma cells.
Long-term humoral immunity is maintained by the formation of high-affinity class-switched memory B cells and long-lived antibody-secreting plasma cells. In healthy humans, a substantial fraction of IgG-positive memory B cells express self-reactive and polyreactive IgG antibodies that frequently develop by somatic mutations. Whether self- and polyreactive IgG-secreting B cells are also tolerated in the long-lived plasma cell pool is not known. To address this question, we cloned and expressed the Ig genes from 177 IgG-producing bone marrow plasma cells of four healthy donors. All antibodies were highly mutated but the frequency of self- and polyreactive IgG antibodies was significantly lower than that found in circulating memory B cells. The data suggest that in contrast to the development of memory B cells, entry into the bone marrow plasma cell compartment requires previously unappreciated selective regulation by mechanisms that limit the production of self- and polyreactive serum IgG antibodies.
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Johannes F
JF
Scheid
Hugo
H
Mouquet
Juliane
J
Kofer
Sergey
S
Yurasov
Michel C
MC
Nussenzweig
Hedda
H
Wardemann
D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007156:Immunologic Memory; D010950:Plasma Cells / Q000276:immunology*; D016133:Polymerase Chain Reaction
D007074:Immunoglobulin G