Complete absence of the fourth component of complement has been described in man and in guinea pigs. Recently, a close linkage between the gene(s) controlling synthesis of C4 and the major histocompatibility complex has been demonstrated in man as well as in the guinea pig.

Because of a possible relationship between immune responses and the complement system, we have studied antibody responses to a T cell dependent antigen in a patient and in guinea pigs with C4 deficiency. Bacteriophage Φχ 174, given intravenously, was cleared within one week after primary injection, similar to normal controls. The primary antibody response was markedly suppressed and shortened: in normal controls, antibody titers (mean Kv > 8) persisted for over 4 weeks; in C4 deficiency, antibody (peak titer < 1) disappeared 2–3 weeks following immunization. In the normal control population, a second injection of antigen resulted in a rapid rise of antibody (Kv > 100) and transition from IgM to IgG.

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