From tumor tissues to autoimmunity: discovery of regulatory DN1 B cells reveals shared pathways of immune regulation.

Claudia Mauri , Isabella Withnell , Zara Baig, Hannah F. Bradford, Joseph C.F. Ng, Antonio
Rullan, Alessandro Di Tullio, Maxine G.B. Tran, Franca Fraternali .
University College London

B cells play central roles in regulating immune responses across a broad spectrum of diseases, including autoimmunity and cancer. In autoimmune conditions such as systemic lupus erythematosus (SLE), expansion of double-negative (DN) B-cell populations has been
strongly associated with pathogenic immune activation and disease severity. In parallel, B cells infiltrating tumors can influence antitumor immunity or contribute to immune suppression within the tumor microenvironment. Despite their importance in both contexts, the diversity and functional specialization of B cell subsets remain incompletely understood. Most current knowledge of human B cell heterogeneity derives from studies of circulating cells. However, immune regulation is largely orchestrated within tissues, where local signals can shape functional B-cell states that may not be represented in peripheral blood. This represents an important gap in our understanding of human B cell biology, one that is increasingly being addressed through the study of tissue samples available from cancer.

In this talk, I will present new data from renal cell carcinoma highlighting differences in B cell composition and functional states across tissues, cancers, and blood. In particular, we identify regulatory B cell populations within tumors and discuss emerging insights into the
role of double-negative B cells in cancer compared with autoimmunity. These findings illustrate how studying B cells directly in tissues can reveal previously unrecognized immune programs with relevance for both tumor immunity and autoimmune disease.