Effects of Mycobacterium tuberculosis liposaccharide ManLAM on CE protein-induced B cell activation

Abstract

Objective To investigate the influence and potential mechanism of mannose-capped lipoarabinomannan (ManLAM) to B cells responding to Mycobacterium tuberculosis (Mtb) infection. Methods B cells were separated from patients with active pulmonary tuberculosis using magnetic beads and then stimulated with ManLAM in combination with CE protein. Flow cytometry was performed to evaluate the apoptosis, proliferation and activation of B cells. The secretion of cytokines and CE protein-specific IgG subclasses were detected by ELISA. ELISPOT assay was used to analyze the influence on the differentiation of B cells into CE protein-specific antibody-secreting cells (ASCs). Results ManLAM inhibited the CE protein-induced proliferation and activation of B cells and the production of pro-inflammatory cytokines, resulting in significantly increased secretion of the immunosuppressive cytokine IL-10. It also inhibited the differentiation of B cells into CE protein-specific IgG secretory cells, but had no significant influence on the differentiation to IgM secretory cells. Moreover, ManLAM inhibited the secretion of CE protein-specific IgG1 and IgG3 and induced the secretion of immunosuppressive IgG4 via TLR2. Conclusions This study suggested that ManLAM could inhibit the anti-tuberculosis immune response of B cells, which provided new theoretical reference for better understanding the immune escape mechanism in Mtb infection. Key words: Mannose-capped lipoarabinomannan (ManLAM); B cell; TLR2; IgG subclasses