Transglutaminase 2 modulates antigen-specific antibody response by suppressing Blimp-1 and AID expression of B cells in mice.
Tansglutaminase 2 (TG2) mediates post-translational modifications of proteins that are involved in a variety of biological processes. Previous reports suggest an involvement of TG2 in adaptive immune responses. However, little has been elucidated in this regard. We explored, in this study, the role of TG2 in humoral immune response to keyhole limpet hemocyanin (KLH) using TG2(-/-) C57BL/6 mice. After primary and secondary immunization with KLH, the serum titer of the antigen-specific antibody was higher in the TG2(-/-) mice than in the wild-type mice. Not only the amount of the specific antibody was increased, but also the affinity of the antibody was estimated as higher in these mice. The TG2(-/-) spleen showed an enhanced germinal center response with higher percentages of GL7(+) germinal center B cells and B220(low) CD138(high) plasma cells. In addition, germinal center B cells from TG2(-/-) mice showed an increased expression of B lymphocyte induced maturation protein-1 (Blimp-1) as well as activation-induced cytidine deaminase (AID). Our results, in sum, indicate a regulatory role of TG2 in humoral immune response to a protein antigen, probably by way of modulating the expression level of proteins related to humoral immune reposes.
Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Jin-Hee
JH
Kim
Eui Man
EM
Jeong
Young-Joo
YJ
Jeong
Wang Jae
WJ
Lee
Jae Seung
JS
Kang
In-Gyu
IG
Kim
Young-Il
YI
Hwang
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D014157:Transcription Factors / Q000235:genetics*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D000941:Antigens; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D006433:Hemocyanins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D003564:Cytidine Deaminase; D019204:GTP-Binding Proteins; C032808:keyhole-limpet hemocyanin