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.

Isotype commitment in the in vivo immune responses. I. Antigen-dependent specific and polyclonal plaque-forming cell responses by B lymphocytes induced to extensive proliferation.

“…Nevertheless, IgG1 is, together with both IgG2 subclasses, one of the most represented isotypes throughout the experiment, in contrast to the other three antibody classes, namely, IgM, IgGz, and IgA, that are poorly or not at all expressed. These results are generally in agreement with previous observations in thymus-dependent immune responses measured in short-term experiments (17)(18)(19). In the context of the present …”

“…Several different mechanisms of independent genetic control have been described to regulate both the primary IgGz, anti-SRBC response in BALB/c and C57B1/10 mice as well as hyperimmune anti-SRBC responses in C57B1/6 and A strains (19). Taken together with our studies, these results suggest that the levels of individual Ig classes produced during primary and hyperimmune responses are regulated by complex mechanisms, in clear contrast to the random recombination and deletion models.…”

“…6). This confirms that a considerable degree of proliferation has taken place in the hyperimmune donors and suggests that, in part, dominant IgG2a production requires extensive "priming" (19). The ratios between specific and nonspecific PFC in hyperimmune cells decline during the experiment (Fig.…”

“…This dependence of subclass expression upon the immunization protocol might be a reason for different antigen-specific subclass patterns previously described in BALB/c mice (19,24). Several different mechanisms of independent genetic control have been described to regulate both the primary IgGz, anti-SRBC response in BALB/c and C57B1/10 mice as well as hyperimmune anti-SRBC responses in C57B1/6 and A strains (19).…”

Analysis of the murine sperm surface with monoclonal antibodies

“…It has been reported that H-Y antigen is limited in distribution to the region of the acrosomal cap in mouse spermatozoa (Koo, Stackpole, Boyse, Hämmerling & Lardis, 1973). The antigen recognized by antibody MS-1 is also confined to the acrosomal region of the sperm head but was not detected on adult male spleen, epidermis or thymus tissues which are H-Y positive in transplantation and serological assays (Gasser & Silvers, 1972;Wachtel, 1977 (Silver & Winn, 1973;Haber & Winn, 1981 (Fellous, Gachelin, Buc-Caron, Dubois & Jacob, 1974). The application of homogeneous antibodies produced in vitro by hybridoma technology after appropriate immunization and screening will largely circumvent the first of these problems.…”