Natural and induced B‐1 cell immunity to infections raises questions of nature versus nurture

Abstract

Mouse B-1 cells are major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and non-overlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy.

Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease

“…In many respects the therapeutic effects of the fibrils resemble pharmacokinetics of adoptive cell therapy rather than a classic small-molecule therapeutic. The proposed mechanism of the migration of the immune-suppressive cells to secondary lymph organs, where they suppress both circulating inflammatory antigenpresenting cells and T lymphocytes, is consistent with published studies on B-regulatory cells (21,44). The mechanism also argues that this therapeutic approach might be beneficial in a number of systemic inflammatory indications.…”

“…The B10 cells in many of these studies were isolated from the spleen and not the peritoneal cavity, but several authors have argued the similarity of the cell types. Although not identical, the different cells appear to be physiologically similar (20)(21)(22).…”

“…Maximal immune suppression by B10 cells is observed after the cells are activated through Toll-like receptor (TLR) (12,23), CD40 (16), or IL-21 ligation (24), all of which induce both an increase in IL-10 production and an egress of the cells from the peritoneum into secondary lymph organs (21,25). Reduction of symptoms in each of the inflammatory autoimmune diseases correlated with reduction of TNF-α, IL-6, and IFN-γ, a pattern similar to that seen with the administration of the amyloidogenic peptides.…”

Characterization of the Antibody Response after Cervical Spinal Cord Injury

“…44 In addition, they inhibit the emergence of autoreactive IgG responses, thereby conveying protection against detrimental humoral autoimmunity. [45][46][47][48] Splenic B1 cells 49 and a subset of bone marrow B1 cells 50,51 constitute the main sources of circulating natural IgM immunoglobulins. Therefore, it is possible that IgM+ ASCs in the spleen increase as a compensatory mechanism to resolve homeostasis after cSCI.…”

The role of B-1 cells in inflammation

“…showed B-1a B-cells migrate from the pleural space to the lung parenchyma and secrete GM-CSF and polyreactive IgM to confer protection against infection [78]. Such a migration model has also been proposed by Baumgarth et al , which suggests that body cavity B-1a cells circulate throughout the animal in the steady state [79]. Following infection by pathogens, innate inflammatory signals contribute to behavioral changes of B-1a cells in the body cavities and these responder populations migrate to neighboring lymphoid sites [79].…”