Major histocompatibility complex control of the idiotypic network in the MOPC 173 system

摘要

AbstractRegulation of the anti‐idiotypic response against MOPC 173 (M‐173, γ2a, ϰ myeloma of the BALB/c strain) was studied after syngeneic and allogeneic immunizations. The immunogen was M‐173 polymerized with glutaraldehyde, and hemagglutinating titers (HT) were determined with sheep red blood cell‐M‐173. H‐2 regulation of the response was clearly shown in mice having the same Igh‐Cagenes as the immunogen protein. H‐2dmice (BALB/c) are dispersed responders (HT: 80‐81 920) and 30 did not respond. H‐2kmice (BALB.K) are high responders (HT: 10240‐81920), and H‐2bmice (BALB.B) are nonresponders (HT<40). In animals of a non‐BALB background, similar observations were made: Igh‐Ca, H‐2kmice (C58) were responders, whereas Igh‐Ca, H‐2bmice (C57L) did not respond. However, more dispersed HT values for the C58 animals as compared with those of the BALB.K suggest that a second level of regulation by background genes might be superimposed. When alloimmunization was used in strains not expressing the Igh‐Caallotype (b, e, j), animals responded whatever the H‐2 haplotype (b, k, d). In this case, allotypic determinants might play a carrier role. All responder mice consistently made antiidiotypic antibodies as determined by hemagglutination and/or radioimmunoassay. Antibodies against new glutaraldehyde‐induced determinants were also produced but appeared in low amounts in syngeneic immunizations. In allogenic immunizations, various levels of anti‐allotype antibodies were detected.BALB.B (and BALB/c) mice are responders to U‐10 (γ2a,ϰ, BALB/c myeloma), polymerized with glutaraldehyde and can respond to the M‐173 idiotype when they are immunized with M‐173 coupled to a heterologous carrier (a human γ1, ϰ myeloma protein, Kle). The unresponsiveness of BALB.B mice to M‐173 is thus idiotype‐specific and is not due to a defect in the anti‐idiotypic antibody repertoire. Injection of M‐173 before M‐173‐Kle prevents the response to M‐173 but not to Kle, which favors the occurrence of suppressive T cells.Responsiveness is dominantly transmitted in (BALB.B × BALB.K)F1mice which are Igh‐Ca/a, H‐2b/kheterozygotes. Unresponsiveness found with the Igh‐Ca, H‐2bcombination is also observed in (BALB.B × B10)F1which are Igh‐Ca/b, H‐2b/b.Since F1animals between BALB.B and B10.A (3R), (4R) or (5R) are all nonresponders, genes involved in the response to M‐173 are not in the K, I‐A, I‐J, or I‐E subregions.