Interference of B lymphocyte tolerance by prolactin in rheumatic autoimmune diseases

Abstract

Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) are the most common rheumatic autoimmune diseases/disorders (RADs) that affect autologous connective tissues as a result of the breakdown of the self-tolerance mechanisms of the immune system. Prolactin, a glycoprotein hormone, has been known for its crucial role in the pathogenesis of these rheumatic autoimmune diseases. In addition to regulating lymphocyte proliferation and antibody synthesis, prolactin is also responsible for regulating cytokine production. Moreover, it contributes to the breakdown of central and peripheral tolerance mechanisms of B lymphocytes. Given the crucial role of prolactin in the pathogenesis of the mentioned RADs, prolactin may contribute to their pathogenesis by the breakdown of tolerance. In the present study, the key role of prolactin to the breakdown of B lymphocyte tolerance and its possible implication for the pathogenesis of these diseases is discussed. Current literature supports prolactin's role in the breakdown of B lymphocyte central and peripheral tolerance mechanisms, such apoptosis, receptor editing, and also anergy. Therefore, prolactin may contribute to the pathogenesis of RADs by the breakdown of B lymphocyte tolerance. However, more investigations, particularly in RA and SSc animal models, are required to precisely address the pathologic role of prolactin.

Keywords: Autoimmune disease; B lymphocyte; B lymphocyte tolerance; Prolactin; Rheumatic autoimmune disease; Tolerance.

Fig. 1

A schematic representation of V(D)J recombination process for the generation of V(D)J exon. During the V(D)J recombination process, one V gene segment, one D gene segment (if it exists in the gene locus), and one J gene segment are randomly selected and rearranged to form a V(D)J exon. The rearranged V(D)J exon encodes the variable region of the antigenic receptor in B lymphocyte. D: diversity; J: joining; V: variable.

Fig. 2

Tolerance mechanisms of B lymphocytes and their breakdown by prolactin. A. Central tolerance mechanisms of B lymphocytes B. Peripheral tolerance mechanisms of B lymphocytes.