Effect of binding immunoglobulin protein on induction of regulatory B cells with killer phenotype during inflammation and disease

Abstract

Immune responses result from different immune cells acting in synergy to successfully fight infections. This requires a high degree of regulation to prevent excessive production of inflammatory products leading to other disease forms. Regulatory B cells are classified based on surface immunoglobulin expression. These cells are reported to resolve inflammation during chronic or autoimmune diseases. However, during chronic inflammation, their frequencies have been shown to be affected, and they can be induced by exposure to extracellular binding immunoglobulin protein (BiP). This review focuses on the effects on immune cells by extracellular or secreted BiP during various chronic inflammatory responses. For example, cell stress associated with Mycobacterium tuberculosis infection leads to accumulation of unfolded proteins that subsequently activate BiP and its three signal transducers intracellularly. Furthermore, BiP can be translocated from the endoplasmic reticulum to the extracellular environment where it binds immune cells as an autoantigen and leads to functional changes. Immune responses during tuberculosis disease require balanced cell interactions. These include antigen-presenting cells, effector cells and regulatory cells. B lymphocytes can mediate regulatory function during chronic diseases and lead to better disease outcome. These specialized cells mediate this function through both surface and soluble protein expression. Their development can be facilitated by different stimuli including binding immunoglobulin protein. This protein resides in the endoplasmic reticulum where it functions in proper protein folding; however, it can escape this location to the extracellular phase, where it affects immune cell function leading to development of regulatory traits on B cells.