Signaling via the B cell receptor (BCR) is essential for B cell survival and development, and antibody production in both physiological and pathological conditions. The nature of BCR signaling is varied in different subpopulations and developmental stages of B cells and can be classified into tonic, chronic active, and priming signaling (1, 2). Whereas, tonic BCR signaling is required for B cell survival and development, chronic active BCR signaling supports the continuous proliferation of B cell lymphoma cells, and antigen-driven priming signaling is important for the initiation of B cell activation and differentiation into antibody-secreting cells. Although the detailed molecular mechanism underlying diverse BCR signaling patterns has been an elusive question in immunology, our knowledge on this regard has been significantly expanded in recent years due to the development of advanced imaging and next-generation sequencing technologies. The aim of this Research Topic, including seven original research articles and five review articles, is to highlight the current understanding of BCR signaling and its relationship with health and disease.

The BCR-mediated signaling in homeostatic conditions depends on the availability of antigens and is delicately regulated by co-stimulatory and co-inhibitory receptors. Co-inhibitory receptors limit BCR signaling in order to prevent B cells from hyperactivation and maintain B cell homeostasis. Among many inhibitory receptors, the proteins of the Sialic acid binding immunoglobulin-like lectin (Siglec) family play important roles in regulating BCR signaling. Meyer et al. reviews Siglecs in B cells, highlighting the interplays between CD45 and CD22 (Siglec-2), CD22 and Galectin-9, and their influence on BCR signaling. Both CD22 and Siglec-G contain immune receptor tyrosine-based inhibitory motifs (ITIMs) within their cytoplasmic tails and recruit the tyrosine phosphatase SHP1, which inhibits B cell signaling. Whereas, CD22 mainly functions in conventional B cells, Siglec-G inhibit the constitutive BCR signaling in autoreactive B-1a cells, probably by binding in cis to the Cμ1 domain of BCR-IgM in the steady-state through α2, 3-or α2, 6 linked sialic acids (3). To understand the organization of CD22 and its association with the BCR, Wasim et al. investigate the effects of mutations at the glycosylation sites of CD22 on BCR signaling and their results show that mutations of N-glycan sites attenuate CD22 phosphorylation and increase BCR signaling in response to antigenic stimulation. Irons and Lay show that ST6Gal-1, a sialyl-transferase that constructs the α2, 6-sialyl linkage on cell surface and extracellular glycans, is a pro-survival factor for transitional B Cells in mice.