B cell-intrinsic IFN-γ promotes excessive CD11cage-associated B cell differentiation and compromised germinal center selection in lupus mice.

Abstract

CD11cage-associated B cells (ABCs) have emerged as a key component in protective and autoreactive B cell responses. Lupus is an autoimmune disorder linked to reduced efficacy of vaccines and increased susceptibility to infections. Previously, we reported that excessive CD11cABCs not only significantly contribute to autoantibody production but also promote aberrant T cell activation and compromised affinity-based germinal center selection in response to immunization in lupus mice. Yet, the regulation of CD11cABC differentiation is not fully understood. In this study, we show that B cell-intrinsic IFN-γ is required for excessive CD11cABC differentiation in lupus mice. B cell-intrinsic IFN-γ is mainly produced by CD11cABCs. IFN-γ-deficiency leads to decreased expression of ABC characteristic genes. We further show that ablating IFN-γ can normalize T cell overactivation and rescue antigen-specific GC responses in lupus mice. Our study offers insight into the crucial role of B cell-intrinsic IFN-γ in promoting excessive CD11cABC differentiation, which compromises affinity-based germinal center selection and affinity maturation in lupus, providing a potential strategy to normalize vaccine responses in lupus.