Genetic control of the expression of immunoglobulin isotypes in the responses of mice to sheep red blood cells.

Abstract

Studies have been carried out on the genetic control of the expression of individual Ig classes in the responses of A/J (A) and C57BL/6J (B6) mice to sheep red blood cells (SRBC). An isotopic anti-immunoglobulin test employing Ig class-specific reagents was used to measure levels of IgM, IgA, IgG1, IgG2a, IgG2b and IgG3 anti-SRBC antibodies in sera of hyperimmunized mice. Compared with B6 mice, A mice are low IgM and IgA responders but high responders with respect to all IgG subclasses. In (B6 X A)F1 mice low responsiveness was dominant for all Ig classes indicating that IgM and IgA responses are controlled by genes different from those which control IgG subclass responses. Analysis of the responses of [(B6 X A)F1 X A] and [(B10.A X A)F1 X A] backcross mice indicates multigenic control of IgG subclass responses. Expression of IgG2a and IgG3 responses appear to be regulated largely by single genes whose action is modified by genes at other loci; control of IgG1 and IgG2b is, clearly, polygenic with no evidence for major control by any single gene. The magnitude of all IgG subclass responses appears to be regulated by a gene(s) associated with or linked to the IgCH locus. Analysis of the responses of H-2-congenic mice shows that major histocompatibility genes do not have a strong influence on the patterns on IgM and IgG responses in A or B6 mice. The overall results indicate that while there is some common control of all IgG classes, there is also separate polygenic control of individual Ig classes.