Censoring of autoreactive B cell development by the pre-B cell receptor.
Antibody diversity occurs randomly as B cells recombine their immunoglobulin (Ig) heavy- and light-chain genes during development. This process inevitably generates reactivity against self structures, and several mechanisms prevent the development of autoreactive B cells. We report here a role for the pre-B cell receptor, composed of Ig heavy and surrogate light chains, in the negative selection of cells expressing Ig heavy chains with the potential to generate autoantibodies. Surrogate light-chain-deficient (SLC-/-) mice harbored elevated levels of antinuclear antibodies (ANAs) in their serum and showed evidence of escape of pre-B cells expressing prototypic autoantibody heavy chains from negative selection, leading to mature autoantibody secreting CD21-CD23- B cells in the periphery. Thus, the pre-B cell receptor appears to censor the development of certain autoantibody-secreting cells and may represent an important factor in multifactorial autoimmune diseases.
Keenan
Rebecca A
RA
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK.
De Riva
Alessandra
A
Corleis
Björn
B
Hepburn
Lucy
L
Licence
Steve
S
Winkler
Thomas H
TH
Mårtensson
Inga-Lill
IL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis; D051379:Mice; D054420:Pre-B Cell Receptors / Q000276:immunology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology*; D017634:Self Tolerance; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate; D054420:Pre-B Cell Receptors