The role of B-1 cells in inflammation

Abstract

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire-skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules such as interleukin-10, adenosine, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has improved not only our understanding of their phenotypic and ontogenic uniqueness but also their role in various inflammatory diseases including influenza, pneumonia, sepsis, atherosclerosis, inflammatory bowel disease, autoimmunity, obesity and diabetes mellitus. Recent identification of human B-1 cells widens the scope of this field, leading to novel innovations that can be implemented from bench to bedside. Among the vast number of studies on B-1 cells, we have carried out a literature review highlighting current trends in the study of B-1 cell involvement during inflammation, which may result in a paradigm shift toward sustainable therapeutics in various inflammatory diseases.

Keywords: Atherosclerosis; Autoimmunity; B-1 cells; IBD; Inflammation; Influenza; Natural IgM; Sepsis.

Figure 1. Role of B-1 cells in inflammatory diseases

B-1 cells recognize endogenous antigens and invading pathogens through B-cell receptor (BCR) or toll-like receptor (TLR)-mediated pathway. Reorganization of Ag causes B-1a cells to migrate from the peritoneal or pleural cavities to the regional lymph nodes or spleen where they may become activated to IgM producing B-cells/memory B-cells. The polyreactive, repertoire skewed natural IgM recognize wide range of endogenous and exogenous Ag to eliminate from the host thus, reducing systemic inflammation. GM-CSF secreting IRA B-cells migrate to the spleen and lungs and confer protection against systemic as well as local S. pneumonia-induced inflammation. By contrast, the IRA B-cells convert Ly6C^lo monocytes to pathogenic Ly6C^hi monocytes in the spleen which then traffic to the atherosclerotic lesions and become atherogenic foam cells, thereby exacerbating atherosclerosis. Apart from B-1 and IRA B-cells, regulatory B-cells play protective roles against various systemic, autoimmune and inflammatory bowel disease by producing immunoregulatory cytokine, IL-10, and natural IgM.