MARKEDLY IMPAIRED HUMORAL IMMUNE-RESPONSE IN MICE DEFICIENT IN COMPLEMENT RECEPTOR-1 AND RECEPTOR-2

Complement receptor 1 (CR1, CD35) and complement receptor 2 (CR2, CD21 ) have been implicated as regulators of B-cell activation, We explored the role of these receptors in the development of humoral immunity by generating CR1- and CR2-deficient mice using gene-targeting technique s. These mice have normal basal levels of IgM and of IgG isotypes. B- and T-cell development are overtly normal, Nevertheless, B-cell respon ses to low and high doses of a T-cell-dependent antigen are impaired,p ith decreased titers of antigen-specific IgM and IgG isotypes. This de fect is not complete because there is still partial activation of B ly mphocytes during the primary immune response, with generation of splen ic germinal centers and a detectable, although reduced, secondary anti body response. These data suggest that certain T-dependent antigens ma nifest an absolute dependence on complement receptors for the initiati on of a normally robust immune response.