Donor Igh-linked genetic control of allotype-specific antibody response

Immunogenicity of allogeneic immunoglobulins in mice were studied, measuring the allotype-specific antibody activity by agglutination of allogeneic antibody-coated red blood cells. It was found that the serum from C.B-20 mice (Ighb, BALB/c-congenic) was uniquely immunogenic in BALB/c mice for allotype antibody response. Whereas the C57BL/6 (Ighb) serum was immunogenic only when heat aggregated and/or combined with adjuvant, the ultracentrifugation-deaggregated C.B-20 serum was definitely immunogenic when administered in a moderate dose (100 microliters/mouse). Even more surprising was the fast that very low doses (0.01-0.1 microliter) of soluble C.B-20 serum, but not C57BL/6 serum, down regulated the allotype-specific response effectively. Genetic analysis on congenic mice suggested that the immunogenicity is controlled by donor Igh or Igh-V (Id-C.B) inasmuch as the serum from BALB/c-congenic C.B-20 (Igh-VbCb), but not BALB/c-congenic BAB/14 (Igh-VaCb), mice was active in BALB/c mice in soluble form. Further studies showed that the Id-C.B was dominantly expressed on the immunoglobulins of (BALB/c x C.B-20)F1 and (C56BL/6 X C.B-20)F1 strains, and was originally derived from the C57BL/Ka strain. The major determinant for the antibody production was encoded in Igh-C, but not in Igh-V. It is suggested that Id-C.B controls the allotype-specific antibody response in an unusual manner, possibly acting as a unique determinant activating helper T cells.