A cohort of highly activated CD99− CD72+ B cells promoting autoimmune progression in juvenile systemic lupus erythematosus

Abstract

CD72 inhibits the development of systemic lupus erythematosus (SLE) by suppressing TLR7-dependent B cell responses to self-nucleic acids (NAs). The absence of CD72 promotes the progression of lupus disease. Here, we find a highly activated subset of CD99⁻ CD72⁺ B cells (CD72⁺ BCs) expressing elevated levels of TLR7 in juvenile SLE, which contributes to autoimmunity. Through multi-omics integrated analysis of single-cell RNA sequencing(scRNA-seq) data and bulk RNA sequencing (RNA-seq) data, we demonstrate that CD72⁺ BCs possess characteristics of both activated naïve B cells (aN) and age-associated B cells (ABCs). Concurrently, CD72⁺ BCs exhibit pronounced plasmablast-like features compared to other cellular subpopulations. We propose a plausible conclusion that CD72⁺ BCs represent a critical transitional cell population involved in the activation and subsequent plasma cell differentiation of naïve B cells and age-related B cells following exposure to self-antigens in SLE. This finding offers novel opportunities for elucidating the genesis of autoantibody-secreting cells involved in the autoimmune response processes in lupus.