B cells and antibodies in the defense against Mycobacterium tuberculosis infection

Abstract

Better understanding of the immunological components and their interactions necessary to prevent or control Mycobacterium tuberculosis (Mtb) infection in humans is critical for tuberculosis (TB) vaccine development strategies. Although the contributory role of humoral immunity in the protection against Mtb infection and disease is less defined than the role of T cells, it has been well-established for many other intracellular pathogens. Here we update and discuss the increasing evidence and the mechanisms of B cells and antibodies in the defense against Mtb infection. We posit that B cells and antibodies have a variety of potential protective roles at each stage of Mtb infection and postulate that such roles should be considered in the development strategies for TB vaccines and other immune-based interventions.

Keywords: B lymphocytes; antibodies; immunity; immunoglobulins; tuberculosis.

Fig. 1

Scheme showing the pathogenesis of tuberculosis and steps where antibody (Ab) and B cells could conceivably provide protection based on literature reports of B cell and Ab action against M. tuberculosis (Mtb) infection. A) Ab could potentially affect the outcome of infection in the alveolar space through opsonization, complement activation, and FcR-mediated enhanced Mtb phagocytosis and killing. Ab could contribute defense mechanisms at the alveolar level during the initial state of infection when inflammation would increase serum permeability and allow the transfer of Abs and complement into the alveolar space; B) B cells located at the germinal center of lymphoid organs could play a role in the defense against infection through i) their function as antigen presenting cells and activation of T cells, ii) production of cytokines that could influence the development of the T helper response, and iii) production of Abs which could modulate various aspects of the innate and adaptive immune response, and clear immunomodulatory Mtb antigens by forming immune complexes; and C) Influence of B cells and Ab on the Abs on the inflammatory response, FcR-mediated phagocytosis and killing of extracellular Mtb within the cavity. Ab could affect granuloma formation through its intrinsic pro- and anti-inflammatory effects. Formation of better organized granulomas in the presence of Ab could potentially translate into reduced dissemination and local control of infection.