Regulation of thymus-dependent and thymus-independent production of immunoglobulin G subclasses by Galpha12 and Galpha13

Abstract

Background: A previous study from this laboratory showed that Gα12 members participate in the production of inflammatory cytokines. In spite of the identification of B cell homeostasis responses regulated by Gα13, the functional roles of Gα12 members in the production of immunoglobulin (Ig) isotypes remained unknown. This study investigated whether Gα12 members are involved in the Ig isotype antibody production with the purpose of establishing their functions in thymus-dependent and thymus-independent humoral responses. Results: Mice lacking Gα12 and/or Gα13 showed an impaired antigen-specific antibody production promoted by challenge(s) of ovalbumin or trinitrophenyl-lipopolysaccharide (TNP-LPS), used for thymus-dependent and thymus-independent stimuli, respectively. Homozygous knockout (KO) of Gα12 or double heterozygous KO of Gα12/Gα13 significantly reduced the antigen-specific total IgG level after multiple ovalbumin immunizations with decreases in the production of IgG1, IgG2a and IgG2b subclasses, as compared to wild type control. In contrast, IgM production was not decreased. Moreover, mice deficient in Gα12 or partially deficient in Gα13 or Gα12/Gα13 showed significantly low production of IgG2b in response to TNP-LPS. In TNP-LPS-injected mice, IgG1 and IgG2a productions were unaffected by the G protein KOs. Conclusion: Our results demonstrate that both Gα12 and Gα13 are essentially involved in thymus-dependent and independent production of IgG subclasses, implying that the G-proteins contribute to the process of antigen-specific IgG antibody production.