Enhanced humoral immune responses against T-independent antigens in Fcα/μR-deficient mice

Honda, Shin‐ichiro; Naoki, Katsuhiko; Miyamoto, Akitomo; Cho, Yukiko; Usui, Kenta; Takeshita, Kie; Takahashi, Satoru; Yasui, Teruhito; Kikutani, Hitoshi; Kinoshita, Taroh; Fujita, Teizo; Tahara‐Hanaoka, Satoko; Shibuya, Kazuko; Shibuya, Akira

doi:10.1073/pnas.0809917106

Cited by 63 publications

(59 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 In this experiment, we detected IgG 3 rather than IgG 1 , because IgG 3 is the subclass raised by T-independent antigens. 21 We found that IRI-treated mice had no increase in IgG 3 specific for NP-ficoll ( Figure 4B). Therefore, T cell processing of antigen seems to be necessary for the amplification of humoral immunity after renal IRI.…”

Section: Renal Iri Requires T Cell Activation and Signaling And T Celmentioning

confidence: 83%

Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response

Fuquay

Renner²,

Kulik

et al. 2013

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Renal transplant recipients who experience delayed graft function have increased risks of rejection and long-term graft failure. Ischemic damage is the most common cause of delayed graft function, and although it is known that tissue inflammation accompanies renal ischemia, it is unknown whether renal ischemia affects the production of antibodies by B lymphocytes, which may lead to chronic humoral rejection and allograft failure. Here, mice immunized with a foreign antigen 24-96 hours after renal ischemia-reperfusion injury developed increased levels of antigen-specific IgG 1 compared with sham-treated controls. This amplified IgG 1 response did not follow unilateral ischemia, and it did not occur in response to a T-independent antigen. To test whether innate immune activation in the kidney after ischemia affects the systemic immune response to antigen, we repeated the immunization experiment using mice deficient in factor B that lack a functional alternative pathway of complement. Renal ischemia-reperfusion injury did not cause amplification of the antigen-specific antibodies in these mice, suggesting that the increased immune response requires a functional alternative pathway of complement. Taken together, these data suggest that ischemic renal injury leads to a rise in antibody production, which may be harmful to renal allografts, possibly explaining a mechanism underlying the link between delayed graft function and longterm allograft failure.

show abstract

Section: Renal Iri Requires T Cell Activation and Signaling And T Celmentioning

confidence: 83%

Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response

Fuquay

Renner²,

Kulik

et al. 2013

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…The finding of elevated serum IgM in naïve Fcmr KO mice is remarkable. Because serum IgM was not affected in mice with null mutations of other IgM-binding receptors, pIgR on mucosal epithelial cells or Fcα/μR on follicular dendritic cells (18,19), the FcμR appears to be the sole receptor in this family that may be involved in maintenance of serum IgM levels within the physiological range. Because the half-life of the injected IgM is the same in Fcmr KO and WT control mice, FcμR does not appear to be involved in IgM catabolism likely mediated by LSECs, but rather is involved in the production and/or secretion of IgM by B and/or plasma cells.…”

Section: Discussionmentioning

confidence: 99%

Altered Ig levels and antibody responses in mice deficient for the Fc receptor for IgM (FcμR)

Honjo

Kubagawa

Jones

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

125

View full text Add to dashboard Cite

Cell surface Fc receptor for IgM antibody (FcμR) is the most recently identified member among FcRs. We determined the cellular distribution of mouse FcμR and the functional consequences of Fcmr disruption. Surface FcμR expression was restricted to B-lineage cells, from immature B to plasma cells, except for a transient downmodulation during germinal center reactions. Fcmr ablation had no significant effect on overall B-and T-cell development, but led to a reduction of marginal zone B cells and an increase in splenic B1 B cells. Preimmune serum IgM in mutant mice was significantly elevated as were natural autoantibodies. When immunized with live attenuated pneumococci, mutant mice mounted robust antibody responses against phosphorylcholine, but not protein, determinants compared with wild-type mice. By contrast, upon immunization with a hapten-carrier conjugate, nitrophenyl-coupled chicken γ-globulin (NP-CGG), the mutant mice had a diminished primary IgG1 response to both NP and CGG. These findings suggest that FcμR has an important role in IgM homeostasis and regulation of humoral immune responses.natural antibody | B-cell tolerance | B-cell subset | autoimmunity

show abstract

“…CD351 mediates the endocytosis of IgA and IgM, therefore playing a pivotal role in systemic and mucosal immunity [18]. Moreover, studies using CD351-deficient mice have demonstrated that this molecule regulates humoral immune responses against T-independent antigens [19].…”

Section: Fc Receptor Familymentioning

confidence: 99%