Late Infection - B-Cell Responses

The role that B cells play in mycobacterial infec­tions is not well understood and is understud­ied based upon the assumption that antibodies are not useful against intracellular pathogens.

Although secretion of antibody is considered a main role, B cells also act as professional antigen-presenting cells and play a crucial role in T-cell activation. It has now become clear that B-cell diversity resembles that of the T-cell sub­sets. B cells can be divided into subpopulations, including naive B cells, immature B cells, plasma cells, regulatory B cells (Bregs) and memory B cells based upon lineage and differentiation markers (Moir and Fauci, 2009). Therefore, it reasonable to assume that B cells responsible for T-cell activation may critically determine the final fate and direction of the ensuing T-cell re­sponse. Evidence has been presented indicating a regulatory role for B cells in chronic inflam­matory pathogenesis that is mediated through IL-10 secretion (Lampropoulou et al., 2008). Upon aerosol infection with M. tuberculosis, B cell-/- mice had higher IL-10 production, bac­terial burden and increased immunopathology in the lungs (Maglione et al., 2007). Previously, a significant increase in B-cell numbers was noted in naturally infected cows demonstrat­ing clinical signs of paratuberculosis as com­pared with subclinical cows or healthy controls (Waters et al., 1999). In cattle, the expansion of a CDS^brlght subpopulation of B cells, suggestive of the B1a population, in the peripheral blood of cattle subclinically infected with MAP has been described (Stabel and Khalifeh, 2008). This find­ing suggests that a shift in the B-cell subpopula­tions is taking place during infection, which may directly or indirectly affect pathogenesis induced by inflammatory T cells. In human TB, the role of B cells is currently being reevaluated as re­viewed recently (Akhbar et al., 201S).

They ar­gue that in TB, antibody could potentially affect the outcome of infection in the alveolar space through opsonization, complement activation and FcR-mediated enhanced M. tuberculosis phagocytosis and killing. Inflammation at the alveolar level during the initial state of infection would increase serum permeability and allow the transfer of antibodies and complement into the alveolar space. B cells located at the germi­nal centre of lymphoid organs could play roles in the defence against infection as professional antigen-presenting cells and T-cell activators; via induction of cytokines with further T-cell expansion; and by clearing immunomodulatory M. tuberculosis antigens by forming immune complexes. Antibody could also affect granu­loma formation through its intrinsic pro- and anti-inflammatory effects. Formation of better organized granulomas in the presence of an­tibody could potentially translate into reduced dissemination and local control of infection (Akhbar et al., 201S). A recent study comparing active TB with latent TB infection (LTBI) in hu­man patients revealed reduced B-cell function in LTBI patients. Moreover, these results indicated that normally functioning B cells, present in treated TB patients, are critical for optimal ac­tivation of human M. tuberculosis-specific T-cell immunity (Joosten et al., 2016). Based upon these observations it can be hypothesized that the late or delayed activation of B cells and pro­duction of antibodies may be an intrinsic part of the pathogenic mechanisms of mycobacteria. The fact that a number of vaccination as well as antibody transfer studies indicate protective ef­fects of antibodies also highlights the need to fur­ther study the role of B cells and antibody during mycobacterial infection (Chan etal., 2014; Koets et al., 201S). Beneficial effects of therapeutic heat shock protein 70 (Hsp 70) vaccination in cattle with naturally acquired chronic MAP in­fection were significantly associated with the ability of the host to mount specific antibody responses, rather than with induction of spe­cific Th1 cells (Santema et al., 2013). Together these observations suggest that the interaction of B cells and T cells is an integral component in the host response to mycobacterial infection and that B cells play a role in regulating pathogenesis of infection.

17.9

More on the topic Late Infection - B-Cell Responses:

1. Late Infection - T-Cell Responses
2. Transition From Early to Late Infection - T-Cell Subpopulations
3. Late Infection - T Regulatory Cells
4. HOST IMMUNE CELL INFECTION WITH HIV
5. CELL DEATH PATHWAY DURING ACUTE HIV-1 INFECTION
6. NEURONAL CELL DEATH IN HIV-1 INFECTION
7. Alfano Massimo (ed.). Soluble Factors Mediating Innate Immune Responses to HIV Infection. Bentham Books,2010. — 159 p., 2010
8. Early Infection - Macrophage- T-Cell Interaction
9. Badley A.D. (ed.). Cell Death During HIV Infection. Taylor & Francis,2006. — 511 p., 2006
10. Cell Death in HIV Infection: gp120
11. 19 T Cell Dynamics and the Role of Apoptosis in HIV Infection