Therapeutic B cell depletion impairs adaptive and autoreactive CD4⁺T cell activation in mice

Abstract

CD20 antibody depletion of B lymphocytes effectively ameliorates multiple T cell-mediated autoimmune diseases through mechanisms that remain unclear. To address this, a mouse CD20 antibody that depletes >95% of mature B cells in mice with otherwise intact immune systems was used to assess the role of B cells in CD4 ؉ and CD8 ؉ T cell activation and expansion in vivo. B cell depletion had no direct effect on T cell subsets or the activation status of CD4 ؉ and CD8 ؉ T cells in naive mice. However, B cell depletion impaired CD4 ؉ T cell activation and clonal expansion in response to protein antigens and pathogen challenge, whereas CD8 ؉ T cell activation was not affected. In vivo dendritic cell ablation, along with CD20 immunotherapy, revealed that optimal antigen-specific CD4 ؉ T cell priming required both B cells and dendritic cells. Most importantly, B cell depletion inhibited antigen-specific CD4 ؉ T cell expansion in both collagen-induced arthritis and autoimmune diabetes mouse models. These results provide direct evidence that B cells contribute to T cell activation and expansion in vivo and offer insights into the mechanism of action for B cell depletion therapy in the treatment of autoimmunity.autoimmune disease ͉ B lymphocyte ͉ immunotherapy ͉ antigen presentation

B Cells Limit Repair after Ischemic Acute Kidney Injury

“…That B cell trafficking preceded T cell trafficking during repair suggests that B cells could be involved in regulating T cell infiltration and expansion in postischemic kidney. An important role of B cells as antigen-presenting or co-stimulatory cells was also reported in animal models of autoimmune disease 30 ; however, adoptive B cell transfer into MT mice did not affect T cell trafficking into the postischemic kidneys, suggesting that B cells could be acting on tubular repair independent of T cell trafficking.…”

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

“…CD20 C B cells contribute both to humoral immunity as antibody-producing cells, but also to cellular immunity by serving as antigen-presenting cells (APCs) and/or by providing costimulatory signals to T cells. 19,20 A favorable effect of tumor-infiltrating B cells on patient prognosis was previously reported in cutaneous melanoma, 21 breast cancer 22 and ovarian cancer, 23 but the mechanism linking the accumulation of these cells in the tumor microenvironment and better prognosis remains poorly understood. Nielsen et al found that tumor-infiltrating B cells expressed markers of antigen presentation and could have a function of professional APCs to support the T cell-mediated immune anticancer response.…”

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

“…However, B cells can influence T cell function through a variety of means (21,(34)(35)(36)(37)(38). It has been suggested that they are involved in regulating the activation status and number of effector T lymphocytes based on observations of abnormal CD4 ϩ T cell responses in B cell-deficient mice (36, 37).…”