Short report

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

Song Jin Lee^1,2 , Woo Hyung Lee¹ , Chang Ho Lee³ and Sang Geon Kim¹

¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea

²Yuhan Corp., Daebang-dong, Dongjak-gu, Seoul 156-754, Korea

³Department of Pharmacology and Institute of Biomedical Science, College of Medicine, Hanyang University, Seoul 133-791, Korea

author email corresponding author email

Journal of Molecular Signaling 2008, 3:12doi:10.1186/1750-2187-3-12

Published:	12 July 2008

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.