Regulation of thymus-dependent and thymus-independent production of immunoglobulin G subclasses by Galpha(12 )and Galpha(13)

BACKGROUND: A previous study from this laboratory showed that Gα(12 )members participate in the production of inflammatory cytokines. In spite of the identification of B cell homeostasis responses regulated by Gα(13), the functional roles of Gα(12 )members in the production of immunoglobulin (Ig) isotypes remained unknown. This study investigated whether Gα(12 )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 Gα(12 )and/or Gα(13 )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 Gα(12 )or double heterozygous KO of Gα(12)/Gα(13 )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 Gα(12 )or partially deficient in Gα(13 )or Gα(12)/Gα(13 )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 Gα(12 )and Gα(13 )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.