Innate Response Activator B Cells Protect Against Microbial Sepsis

Abstract

Recognition and clearance of bacterial infection is a fundamental property of innate immunity. Here we describe an effector B cell population that protects against microbial sepsis. Innate response activator (IRA)-B cells are phenotypically and functionally distinct, develop and diverge from B1a B cells, depend on pattern recognition receptors, and produce GM-CSF. Specific deletion of IRA-B cell activity impairs bacterial clearance, elicits a cytokine storm, and precipitates septic shock. These observations enrich our understanding of innate immunity, position IRA-B cells as gatekeepers of bacterial infection, and identify new treatment avenues for infectious diseases.

Re-thinking the functions of IgA+plasma cells

“…1 Importantly, B lineage-specific expression of the innate immune effector molecules TNFa and iNOS was shown to be required for IgA C PC homeostasis at steady-state and during infection. In addition to our study, new and unexpected functions have been ascribed to IgA C PC independent of Ab secretion, [2][3][4] suggesting that this important mucosal cell type should be re-examined in the context of inflammation and infection. We outline here mechanisms of IgA C PC generation and survival, reviewing their functions in health and disease, and discuss candidate roles of iNOS and TNFa in the context of IgA C PC.…”

“…For example, an innate and rapid anti-microbial response has been shown to be associated with the production of GM-CSF by plasmablasts. 4 In addition, a PC population has been shown to produce IL-17A in response to a parasitic infection. 3 The accumulation of IgA C PC in some disease settings such as athlerosclerosis 153 implores one to consider if IgA C PC in these locations are exerting effects via their secretion of Abs or perhaps via other Abindependent functions or both.…”

Dynamics of the Splenic Innate-like CD19+CD45Rlo Cell Population from Adult Mice in Homeostatic and Activated Conditions

“…5A). Finally, TLR4 activation, which promotes the secretion of GM-CSF by IRA cells (9), failed to induce cytoplasmic expression of GM-CSF by 19 + 45R lo cells (Fig. 6D).…”

“…For in vivo GM-CSF detection, injections of LPS (10 mg/ ml) were performed with four daily i.p. injections of LPS as described previously (9), and the cytoplasmic detection was as indicated above for IL-10.…”

“…B-1 and MZ cells share some characteristic features such as the oligoclonality of their BCRs (1, 2), Agindependent selection (3), their distribution in particular niches, a preactivation status that is responsible for their rapid multispecific responses (4), and their participation in maintaining homeostasis and in the initial phases of the immune response (5). Recently, several new innate like B lymphocytes have been described, such as age-associated B cells (ABCs) (6,7), gut-associated B cells (8), and innate response activator (IRA) cells (9), which are implicated in autoimmune disorders and the responses to microbial infection.…”