International Immunology Advance Access originally published online on February 14, 2005
International Immunology 2005 17(4):343-350; doi:10.1093/intimm/dxh214
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Stochastic pairing of Ig heavy and light chains frequently generates B cell antigen receptors that are subject to editing in vivo
1 Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany
2 Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore
3 Present address: Biogen Idec, MA 02142, USA
4 Present address: National Institute for Longevity Sciences, 474-8522 Aichi, Japan
5 Present address: Bayer Healthcare AG, 51368 Leverkusen, Germany
6 Present address: National Jewish Medical and Research Center, Denver, CO 80206, USA
Correspondence to: K.-P. Lam; E-mail: mcblamkp{at}imcb.nus.edu.sg
We examined the generation and selection of the B cell antibody repertoire through crossing of mice bearing distinct Ig heavy (H) and light (L) chain rearranged variable region transgenes. Ig gene knock-in and transgenic mice whose H and L chains pair to form a non-autoreactive, functional B cell antigen receptor (BCR) have significantly reduced pre-B cells in the bone marrow as their B cell progenitors rapidly differentiate into surface IgM+ B cells. The presence of a pre-B cell compartment in these Ig transgenic mice, however, indicates the induction of receptor editing. Here, 18 distinct combinations of H and L chains were generated that we showed could pair in vitro to form BCRs of unknown specificities. Of these, nine induced receptor editing in vivo as evidenced by the presence of pre-B cells and endogenous L chain rearrangements in mice bearing these H and L chain transgenes. These data thus suggest that about half of the emerging antibody repertoire is negatively selected during B lymphopoiesis due to the likely encoding of autoreactive or non-functional BCRs.
Keywords: antibody repertoire, autoimmunity, B cell development, gene targeting, receptor editing
Transmitting editor: D. Tarlinton
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