Innate-like B cell subsets during immune responses: Beyond antibody production

Abstract

B lymphocytes are recognized for their crucial role in the adaptive immunity since they represent the only leukocyte lineage capable of differentiating into Ab‐secreting cells. However, it has been demonstrated that these lymphocytes can exert several Ab‐independent functions, including engulfing and processing Ags for presentation to T cells, secreting soluble mediators, providing co‐stimulatory signals, and even participating in lymphoid tissues development. Beyond that, several reports claiming the existence of multiple B cell subsets contributing directly to innate immune responses have appeared. These “innate‐like” B lymphocytes, whose phenotype, development pathways, tissue distribution, and functions are in most cases notoriously different from those of conventional B cells, are crucial to early protective responses against pathogens by exerting “crossover” defensive strategies that blur the established boundaries of innate and adaptive branches of immunity. Examples of these mechanisms include the rapid secretion of the polyspecific natural Abs, increased susceptibility to innate receptors‐mediated activation, cytokine secretion, downstream priming of other innate cells, usage of specific variable immunoglobulin gene‐segments, and other features. As these new insights emerge, it is becoming preponderant to redefine the functionality of B cells beyond their classical adaptive‐immune tasks.

Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

“…BCR signal pathways positively modulate the function of innate-like B cells [79]. Deficiency of BCR signal inhibitory coreceptors CD22 and Sialic acid-binding immunoglobulin-type lectin-G (Siglec-G) led to the significant expansions of B-1 cells and MZ B cells, together with lupus-like systemic autoimmune development in mice [80].…”

B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients

“…B cells’ ability to differentiate into plasma cells that produce a vast antibody repertoire that protects against almost every potential pathogen, and at the same time, the generation of immunological memory available to suppress subsequent infections, represent the most recognized functions of these lymphocytes ( 21 ). However, B cells have also been implicated in pathogenic roles in autoimmune diseases, transplant, cancer, or even infections, exerting alternative antibody-independent responses that often rely on cytokine secretion with either, pro- or anti-inflammatory properties ( 22 ). Circulating human B cells are typically classified into different compartments that include immature recent bone marrow emigrants (transitional B cells), mature lymphocytes never-stimulated by their cognate antigen (naïve B cells), and terminally differentiated cells that resulted from previous immune responses due to antigen exposure (memory B cells and antibody-secreting plasmablasts/plasma cells); all of them with derived phenotypical and functional divergent subsets ( 22 ).…”

“…However, B cells have also been implicated in pathogenic roles in autoimmune diseases, transplant, cancer, or even infections, exerting alternative antibody-independent responses that often rely on cytokine secretion with either, pro- or anti-inflammatory properties ( 22 ). Circulating human B cells are typically classified into different compartments that include immature recent bone marrow emigrants (transitional B cells), mature lymphocytes never-stimulated by their cognate antigen (naïve B cells), and terminally differentiated cells that resulted from previous immune responses due to antigen exposure (memory B cells and antibody-secreting plasmablasts/plasma cells); all of them with derived phenotypical and functional divergent subsets ( 22 ). Recently, the development of new powerful multiparametric flow cytometric and single-cell genomic approaches, has allowed the identification of emerging B cell populations with distinctive phenotypical and functional characteristics ( 23 – 25 ).…”

“…Recently, the development of new powerful multiparametric flow cytometric and single-cell genomic approaches, has allowed the identification of emerging B cell populations with distinctive phenotypical and functional characteristics ( 23 – 25 ). Since many of these cells have been implicated in the pathogenesis of acute and chronic viral infections ( 22 ), we become interested in mapping them in COVID-19 patients, trying to find a link between their presence and the clinical presentations of this globally relevant disease.…”

Effect of theTc13Tul antigen fromTrypanosoma cruzion splenocytes fromnaïvemice

“…In the spleen, B-1 and marginal zone B cells have shown to be the main source of T-independent production of IgM antibodies in the early stage of the immune response, although they are also able to undergo IgG class switching (Martin et al ., 2001). These B lymphocyte subsets, classified as ‘innate-like’ B cells, act as sentinels to rapidly respond to blood-borne antigens by expressing polyreactive less specific B-cell receptors and having rapid proliferation rates (Romero-Ramírez et al ., 2019). The basal level of non-specific IgM secretion by splenocytes from Tc 13Tul-inoculated mice and the additive effect observed when they are in vitro stimulated with Tc 13Tul suggest that the primary immune mechanism triggered by Tc 13Tul may include stimulation of innate-like B cells.…”