Efficient generation of B lymphocytes by recognition of self‐antigens

• Published in: European journal of immunology Vol. 41; no. 8; pp. 2397 - 2403
• Main Authors: Eschbach, Cathrin, Bach, Martina P., Fidler, Ingrid, Pelanda, Roberta, Köhler, Fabian, Rajewsky, Klaus, Jumaa, Hassan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.08.2011; Wiley Subscription Services, Inc
• Subjects: Animals; Autoantigens - immunology; Autoimmune; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cells, Cultured; Female; Flow Cytometry; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - metabolism; Male; Medical research; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Precursor Cells, B-Lymphoid - immunology; Precursor Cells, B-Lymphoid - metabolism; Proliferation; Receptors, Antigen, B-Cell - immunology; Selection; Self‐reactive; Signal Transduction - immunology; T cell receptors
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201041344

Antibody diversity is generated by a random gene recombination process with the inherent risk of the production of autoreactive specificities. The current view suggests that B cells expressing such specificities are negatively selected at an early developmental stage. Using the knock‐in model system of the 3‐83 autoreactive B‐cell antigen receptor (BCR) in combination with precursor‐BCR (pre‐BCR) deficiency, we show here that the 3‐83 BCR mediates efficient generation of B cells in the presence, but not the absence, of a strongly recognized auto‐antigen. Experiments with mixed bone marrow chimeras showed that combining the 3‐83 BCR with the corresponding auto‐antigen resulted in efficient reconstitution of B‐cell development in immune‐deficient mice. These results suggest that B cells are positively selected by recognition of self‐antigens during developmental stages that precede receptor editing. Moreover, the data indicate that the pre‐BCR functions as a specialized autoreactive BCR to initiate positive selection at a stage where the cells express immunoglobulin heavy but not light chains.