Desensitization of the antigen receptor primes B cells for activation by superstimulatory influenza virus.
Interaction of the B cell receptor (BCR) with non-immunogenic receptor ligands can induce a specific state of B cell unresponsiveness as a result of receptor desensitization. Provided it is maintained over time, BCR desensitization may provide the molecular basis for clonal anergy. Using an in vitro model of anti-Ig-mediated BCR desensitization, we assessed the susceptibility of desensitized "anergic" B lymphocytes to activation by B cell superstimulatory influenza virus hemagglutinin (HA). Rabbit anti-mouse Ig antibodies (whole Ig molecule or F(ab')(2)-fragments) totally abolished the response of murine B cells to HA, when added simultaneously with the virus. Pretreatment with the same antibodies, however, yielding a complete unresponsiveness to a subsequent challenge with normally mitogenic anti-Ig reagents, even enhanced the subsequent proliferative response to HA. By contrast, HA-mediated high-rate immunoglobulin synthesis was suppressed after desensitization. BCR-desensitized, HA-stimulated B cells exhibited a hyperexpression of various activation markers (B7, major histocompatibility complex class II, CD25) and served as potent antigen-presenting cells (APC) in a polyclonal model for T lymphocyte activation. These observations suggest a possible scenario for the breaking of natural B cell tolerance, where infections with B cell superstimulatory viruses may lead to the clonal expansion of receptor desensitized, functionally silenced B lymphocytes in vivo.
Rott
O
O
Hospital Cochin, Universite Rene Descartes, Paris, France.
Charreire
J
J
Cash
E
E
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis
D000888:Antibodies, Anti-Idiotypic; D018122:B7-1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; D015375:Receptors, Interleukin-2