B-1 cell responses to infections

Abstract

B-1 cells represent an innate-like early-developing B cell population, whose existence as an independent lymphocyte subset has been questioned in the past. Recent molecular and lineage tracing studies have not only confirmed their unique origins and differentiation paths, they have also provided a rationale for their distinctive functionalities compared to conventional B cells. This review summarizes our current understanding of B-1 cell development, and the activation events that regulate B-1 cell responses to self and foreign antigens. We discuss the unresolved question to what extent BCR engagement, that is, antigen-specificity versus innate signaling contributes to B-1 cell's participation in tissue homeostasis and immune defense as providers of 'natural' and antigen-induced antibody responses, and as cytokine-producing immune regulators.

Figure 1. Outcomes of B-1 cell activation

Pleural cavity B-1 cells respond to microbial insults by migration to regional lymphoid tissue such as mediastinal lymph nodes and mediastinal fat-associated lymphocyte tissue, whereas peritoneal cavity B-1 cells will migrate to spleen, gut-associated lymphoid tissue and/or omentum. Although B-1 cells circulate continuously in and out of the body cavities, their migration seems enhanced after an insult (left panel). Following arrival in the lymphoid tissues B-1 cells were shown to differentiate into IgM-secreting cells. B-1 cells in the cavities may also spontaneously secrete cytokines, specifically IL-10, or GM-CSF and IL-3 following their arrival in lypmphoid tissues (middle panel). Weeks to months after foreign antigen exposure a higher frequency of antigen-binding B-1 cells accumulate in body cavities, which are otherwise phenotypically indistinguishable from other B-1 cells. Following adoptive transfer of body cavity cells, these cell populations have been shown to provide increased immune protection, i.e. a memory function. It is unresolved whether antigen-stimulated B-1 cells have an enhanced ability to differentiate to antibody-secreting cells, or whether their higher frequencies alone can provide enhanced protection during challenge (right panel).

Figure 2. BCR complex reorganization following B-1 cell stimulation

B-1 cells express surface IgM- but little to no IgD-BCR. In the steady state their IgM-BCR closely associates with CD19 and with CD5. This complex is unable to signal via Igα/β following BCR-antigen stimulatik, however, B-1 cells vigoriously signal strongly following stimulation via TLR (left). Activation of B-1 cells via TLR alters their BCR complex, resulting in loss of CD5-mediated inhibition and BCR-downstream signaling (right). IgM-BCR complex reorganization may explain antigen-specific responses by self-reactive B-1 cells.