Src Family Protein Kinase Controls the Fate of B Cells in Autoimmune Diseases.

Abstract

There are more than 80 kinds of autoimmune diseases known at present, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), inflammatory bowel disease (IBD), as well as other disorders. Autoimmune diseases have a characteristic of immune responses directly attacking own tissues, leading to systematic inflammation and subsequent tissue damage. B cells play a vital role in the development of autoimmune diseases and differentiate into plasma cells or memory B cells to secrete high-affinity antibody or provide long-lasting function. Drugs targeting B cells show good therapeutic effects for the treatment of autoimmune diseases, such as rituximab (anti-CD20 antibody). Src family protein kinases (SFKs) are believed to play important roles in a variety of cellular functions such as growth, proliferation, and differentiation of B cell via B cell antigen receptor (BCR). Lck/Yes-related novel protein tyrosine kinase (LYN), BLK (B lymphocyte kinase), and Fyn are three different kinds of SFKs mainly expressed in B cells. LYN has a dual role in the BCR signal. On the one hand, positive signals are beneficial to the development and maturation of B cells. On the other hand, LYN can also inhibit excessively activated B cells. BLK is involved in the proliferation, differentiation, and immune tolerance of B lymphocytes, and further affects the function of B cells, which may lead to autoreactive or regulatory cellular responses, increasing the risk of autoimmune diseases. Fyn may affect the development of autoimmune disorders via the differentiation of B cells in the early stage of B cell development. This article reviews the recent advances of SFKs in B lymphocytes in autoimmune diseases.