Predominant autoantibody production by early human B cell precursors.
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
Wardemann
Hedda
H
Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA.
Yurasov
Sergey
S
Schaefer
Anne
A
Young
James W
JW
Meffre
Eric
E
Nussenzweig
Michel C
MC
D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D000916:Antibody Diversity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology; D003600:Cytosol / Q000276:immunology; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology; D011995:Recombination, Genetic; D012641:Selection, Genetic; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains