Differences between C4A and C4B in the handling of immune complexes: the enhancement of CR1 binding is more important than the inhibition of immunoprecipitation

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Abstract
SUMMARY: There are two isotypes of C4—C4A and C4B—, encoded within the major histocompatibility complex with quite different properties. In this study we have compared purified C4A and C4B with regard to their ability to prevent immune complex precipitation and to enhance the binding of both preformed and nascent immune complexes to the receptor CR1 on red cells. C4A was modestly more effective than C4B at inhibiting immunoprecipitation, particularly in antibody excess. In the CRI binding assay C4A was markedly more effective than C4B in enhancing binding to CRI. This difference was seen with both preformed and nascent immune complexes at equivalence and antibody excess. Thus the major differences between C4A and C4B in regard to immune complex handling is at the level of CRI binding. Given the strong association of C4A* QO alleles with immune complexmediated diseases like systemic lupus erythematosus, these findings have important pathogenetic implications.