Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control

Khader and colleagues show Mycobacterium tuberculosis (Mtb)-specific B cells are needed to recruit T-FH cells into follicular-like structures within lung granulomas to control the Mtb bacilli; however, specific antibodies and many conventional properties of B cells are dispensable. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the T(H)1 and T(H)17 subsets of helper T cells and follicular helper T (T-FH)-like cellular responses. A population of IRF4(+) T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6(fl/fl)) in CD4(+) T cells (CD4(cre)) resulted in reduction of T-FH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize T-FH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.

Automated summary

Khader and colleagues demonstrate that Mtb-specific B cells play a vital role in recruiting T-FH cells into follicular-like structures within lung granulomas to control Mtb bacilli. However, specific antibodies and conventional properties of B cells are not essential for this process. Understanding the mechanisms of protection during TB is crucial due to its global impact as a leading cause of death.