Genetic control of B-cell function. I. Two genes determine the magnitude of antibody responses of inbred mice to red blood cells |
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Authors: | D Hetzelberger K Eichmann |
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Affiliation: | Institute for Immunology and Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany |
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Abstract: | In this paper we analyze the details of the genetic control of high and low responsiveness to limiting doses of RBC in inbred mice. We find that high and low responsiveness is expressed in several types of antibody responses, is a quantitative phenomenon, and apparently applies to all red blood cell antigens. Using the primary PFC response to SRBC in vitro as test system, we find that inbred mouse strains of independent genetic origin can be classified as high or as low responders. Breeding experiments revealed segregation ratios in F2 and backcross progeny that clearly show a control by 2 independently segregating genes, one of them linked to the Igh gene complex. An analysis of a variety of congenic strains revealed that a high responder Igh gene complex is necessary but insufficient to maintain high responsiveness and that the additional gene required is neither linked to H-2 nor to Lyt-23 (k-chain genes). An analysis of the CXB RI strains confirmed the important role of Igh and suggested that the additional genetic information may be associated with the minor histocompatibility loci H-21 or H-30.In the following paper of this series we show that high and low responsiveness to RBC is exclusively determined by the B cell. Because of the lack of determinant specificity of the response polymorphism we consider the possibility that the role of Igh in the genetic control may not be restricted to encoding specific Ig receptors for RBC. As an alternative, we consider its role as one of two genes with additive or complementing effects in specifying the ability of B cells to become activated in a T-helper-cell-dependent response. Taken together, we think that we have a system at hand to study the mechanism of B-cell activation by a genetic approach. |
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Keywords: | red blood cells sheep red blood cells horse red blood cells bovine red blood cells chicken red blood cells trinitrophenyl group-A streptococcal vaccine plaque-forming cell immunglobulin heavy-chain gene complex major histocompatibility gene complex variable region of Ig heavy chain recombinant inbred |
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