Rheumatoid factor blocks regulatory Fc signals.
Immunosuppressed cultures of murine spleen cells, partly deprived of T cells and antigen-stimulated, can be reconstituted to near full activity in their antibody-forming cell response with murine rheumatoid factors (RF). The dose of RF required for recovery of 50% of the reconstitutable immune response was 10-100 ng and reconstitution was blocked by intact murine IgG added to the cultures. IgG subclass specificity of RF was demonstrated; RF specific for IgG2a was more potent than RF specific for IgG1 in reconstituting the response. Synergy was observed between RF added at culture initiation and late-acting B-cell differentiation factors. The greater the degree of T-cell deprivation, the more stringent the conditions needed for reconstitution. Suitable conditions for reconstitution with profound T-cell depletion included the limited reconstitution by specific RF, the synergistic action of RF with late-acting T-cell-replacing supernatants, and multiple additions of a number of RFs to the cultures on Days 0, 1, and 2. RF was also shown to block Fc-dependent immunosuppression by added antigen-antibody complexes. These results are interpreted as favoring the hypothesis put forward previously that the normal production of RF acts to reduce T-cell dependency by preventing negative Fc signal transmission by immune complexes on the B-cell surface. Abnormal production of RF may be a primary destabilizer of the immune responses leading to autoimmunity.
Panoskaltsis
A
A
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Sinclair
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NR
D000818:Animals; D000918:Antibody Specificity; D004357:Drug Synergism; D005260:Female; D007116:Immunization, Passive; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000502:physiology; D015848:Interleukin-5; D007378:Interleukins / Q000502:physiology; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D012217:Rheumatoid Factor / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D015848:Interleukin-5; D007378:Interleukins; D012217:Rheumatoid Factor