Excessive CD11c⁺Tbet⁺ B cells promote aberrant T_FH differentiation and affinity-based germinal center selection in lupus.

ABSTRACT: Excessive self-reactive and inadequate affinity-matured antigen-specific antibody responses have been reported to coexist in lupus, with elusive cellular and molecular mechanisms. Here, we report that the antigen-specific germinal center (GC) response-a process critical for antibody affinity maturation-is compromised in murine lupus models. Importantly, this defect can be triggered by excessive autoimmunity-relevant CD11c⁺Tbet⁺ age-associated B cells (ABCs). In B cell-intrinsic Ship-deficient (ShipΔB) lupus mice, excessive CD11c⁺Tbet⁺ ABCs induce deregulated follicular T-helper (T_FH) cell differentiation through their potent antigen-presenting function and consequently compromise affinity-based GC selection. Excessive CD11c⁺

SUBMITTER: Zhang W 

PROVIDER: S-EPMC6744857 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature