Abstract
B lymphocytes learn through the interaction of the B cell receptor with antigens in the context of B cell developmental stage and environmental cues. B cells can respond by proliferation and antibody secretion, programmed cell death, or modification of the antibody genes themselves through secondary immunoglobulin gene rearrangements or somatic point mutation. Acritical learning process is that of self/nonself-discrimination. We have shown that one potent mechanism for immune self-tolerance in B cells is ongoing antibody light chain gene rearrangements, which can result in “receptor editing” that gene rearrangements, which can result in “receptor editing” that changes antigen receptor specificity. This process appears to be developmentally regulated, because it is confined to cells at an immature stage of development. Cells at later stages of development can be tolerized by apoptosis, but probably not by receptor editing.
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Karasuyama H, Rolink A, Melchers F: Surrogate light chain in B cell development. Adv Immunol 1996;63:1–41.
Pillai S: The chosen few? Positive selection and the generation of naive B lymphocytes. Immunity 1999;10:493–502.
Storb, U.: Transgenic mice with immunoglobulin genes. Annu Rev Immunol 1987:5:151–174.
Tiegs SL, Russell DM, Nemazee D: Receptor editing in self-reactive bone marrow B cells. J Exp Med 1993;177:1009–1020.
Alt FW, Yancopoulos GD, Blackwell TK, Wood C, Thomas E, Boss M, Coffman R, Rosenberg N, Tonegawa S, Baltimore D: Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J 1984;3: 1209–1219.
Gay D, Saunders T, Camper S, Weigert M: Receptor editing: an approach by autoreactive B cells to escape to lerance. J Exp Med 1993;177:999–1008
Radic MZ, Zouali M: Receptor editing, immune diversification, and self-tolerance. Immunity 1996;5:505–511.
Dunda O, Corcos D: Recombining sequence recombination in normal kappa-chain-expressing B cells. J Immunol 1997;159: 4362–4366.
Nadel B, Cazenave PA, Sanchez P: Murine lambda gene rearrangements: the tochastic model prevails over the ordered model. EMBO J 1990;9:435–440.
Retter MW, Nemazee D: Receptor editing occurs frequently during normal B cell development. J Exp Med 1998;188:1231–1238.
Prak EL, Trounstine M, Huszar D, Weigert M: Light chain editing in kappa-deficient animals: a potential mechanism of B cell tolerance. J Exp Med 1994;180: 1805–1815.
Radic MZ, Erikson J, Litwin S, Weigert M: B lymphocytes may escape tolerance by revising their antigen receptors. J Exp Med 1993; 177:1165–1173.
Chen C, Prak EL, Weigert M: Editing disease-associated autoantibodies. Immunity 1997;6:97–105.
Melamed D, Nemazee D. Selfantigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest. Proc Natl Acad Sci USA 1997;94:9267–9272.
Melamed D, Kench JA, Grabstein K, Rolink A, Nemazee D: A functional B cell receptor transgene allows efficient IL-7-independent maturation of B cell precursors. J Immunol 1997;159:1233–1239.
Melamed D, Benschop RJ, Cambier JC, Nemazee D: Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection. Cell 1998;92: 173–182.
Kench JA, Russell DM, Nemazee D: Efficient peripheral clonalelimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes. J Exp Med 1998; 188:909–917.
Russell DM, Dembic Z, Morahan G, Miller JF, Burki K, Nemazee D:
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Nemazee, D. Role of B cell antigen receptor in regulation of V(D)J recombination and cell survival. Immunol Res 21, 259–263 (2000). https://doi.org/10.1385/IR:21:2-3:259
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DOI: https://doi.org/10.1385/IR:21:2-3:259