TY - JOUR
T1 - Rheumatoid factor blocks regulatory Fc signals
AU - Panoskaltsis, Angela
AU - Sinclair, Nicholas R St C
PY - 1989/10/1
Y1 - 1989/10/1
N2 - 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 antigenantibody 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.
AB - 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 antigenantibody 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.
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U2 - 10.1016/0008-8749(89)90278-5
DO - 10.1016/0008-8749(89)90278-5
M3 - Article
C2 - 2570644
AN - SCOPUS:0024461208
VL - 123
SP - 177
EP - 188
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1
ER -