Memory B cells and tuberculosis

Authors: LYASHCHENKO, KONSTANTIN - Chembio Diagnostic Systems, Inc; VORDERMEIER, H. MARTIN - Animal & Plant Health Agency Apha; WATERS, WILLIAM - Retired ARS Employee

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Literature Review
Publication Acceptance Date: 1/29/2020
Publication Date: 2/1/2020
Citation: Lyashchenko, K.P., Vordermeier, H., Waters, W.R. 2020. Memory B cells and tuberculosis. Veterinary Immunology and Immunopathology. 221(110016). https://doi.org/10.1016/j.vetimm.2020.110016.
DOI: https://doi.org/10.1016/j.vetimm.2020.110016

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in Texas, New Mexico, Indiana, California, and South Dakota as well as recurrence of infection in Michigan demonstrate that the disease is far from eliminated from the United States. Improved techniques are needed for detection of infected cattle as well as improved control strategies (e.g., vaccines). To develop improved tests and vaccines, it is beneficial to first understand the nature of bovine immune responses to the pathogen. In this study, important cell types of cattle involved in the immune response to bovine tuberculosis were characterized in blood samples collected from infected animals. These cells were identified and characterized in terms of function. This basic information will be useful for development of improved tests and vaccines for the control of tuberculosis in cattle.

Technical Abstract: Immunological memory is a central feature of adaptive immunity. Memory B cells are generated upon stimulation with antigen presented by follicular dendritic cells in the peripheral lymphoid tissues. This process typically involves class-switch recombination and somatic hypermutation and it can be dependent or independent on germinal centers or T cell help. The mature B cell memory pool is generally characterized by remarkable heterogeneity of functionally and phenotypically distinct sub-populations supporting multi-layer immune plasticity. Memory B cells found in human patients infected with Mycobacterium tuberculosis include IgD+ CD27+ and IgM+ CD27+ subsets. In addition, expansion of atypical memory B cells characterized by the lack of CD27 expression and by inability to respond to antigen-induced re-activation is documented in human tuberculosis. These functionally impaired memory B cells are believed to have adverse effects on host immunity. Human and animal studies demonstrate recruitment of antigen-activated B cells to the infection sites and their presence in lung granulomas where proliferating B cells are organized into discrete clusters resembling germinal centers of secondary lymphoid organs. Cattle studies show development of IgM+, IgG+, and IgA+ memory B cells in M. bovis infection with the ability to rapidly differentiate into antibody-producing plasma cells upon antigen re-exposure. This review discusses recent advances in research on generation, re-activation, heterogeneity, and immunobiological functions of memory B cells in tuberculosis. The role of memory B cells in postskin test recall antibody responses in bovine tuberculosis and implications for development of improved immunodiagnostics are also reviewed.