B cells: architects of autoimmunity — signaling, memory subsets, and ectopic lymphoid structures

B cells are central architects of immune protection, yet their dysregulation drives the initiation, amplification, and persistence of autoimmune disease. Far beyond their classical role as antibody-producing cells, B cells integrate cues across both innate and adaptive pathways—including B cell receptor engagement, co-stimulatory checkpoints, and Toll-like receptor sensing—to shape chronic immune responses. Through antigen presentation, cytokine secretion, germinal center activity, and cellular crosstalk with T cells and myeloid populations, B cells actively govern local tissue pathology and inflammatory amplification.This Research Topic explores the cellular and molecular mechanisms connecting B cell activation and fate decisions to autoimmune disease progression. Particular emphasis is placed on two pivotal areas of recent momentum: atypical and age-associated memory B cells (such as T-bet+CD11c+ subsets), which expand in systemic autoimmunity and contribute directly to autoantibody-secreting pools, and ectopic lymphoid structures (ELS) within inflamed target tissues, where local B cell activation organizes sustained immune amplification. In addition, advances in targeted interventions—including BTK inhibition, BAFF/APRIL blockade, and B cell-depleting strategies—have underscored the need to resolve how distinct B cell subsets dictate therapeutic response and disease relapse.We welcome the submission of Original Research, Brief Research Reports, Reviews, Mini Reviews, Perspectives, and Methods articles that:• Delineate intracellular B cell receptor signaling networks, with emphasis on Syk-, Btk-, and Lyn-dependent pathways in autoimmune models;• Investigate co-stimulatory checkpoints and cytokine sensing mechanisms, including CD40, BAFF/APRIL, TLR, and JAK-STAT signaling cascades in autoreactive B cells;• Define the origin, transcriptional regulation, and pathogenic roles of age-associated and atypical memory B cells in chronic autoimmune disease;• Analyze the cellular organization and immunological function of ectopic lymphoid structures and tertiary lymphoid organs in inflamed tissues;• Characterize antibody-independent B cell functions, such as antigen presentation and local cytokine/chemokine secretion, in driving tissue inflammation;• Uncover cellular and molecular determinants of plasmablast and autoreactive plasma cell differentiation and long-term persistence;• Examine bidirectional cellular crosstalk between B cells and specialized T cell subsets, particularly T follicular helper (Tfh) and T peripheral helper (Tph) cells; and• Evaluate mechanistic insights and subset dynamics arising from targeted B cell and plasma cell therapies in pre-clinical models and translational clinical studies.Please note: manuscripts that describe clinical disease courses, epidemiological cohorts, or general inflammatory conditions without a clear mechanistic connection to B cell biology fall outside the scope of this collection. Topic editors: Hiroaki Niiro, Anne Satterthwaite Source: https://www.frontiersin.org/research-topics/87120/b-cells-architects-of-autoimmunity---signaling-memory-subsets-and-ectopic-lymphoid-structures