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

Rosemary V. Swanson, Ananya Gupta, Taylor W. Foreman, Lan Lu, Jose Alberto Choreno-Parra, Stanley Kimbung Mbandi, Bruce A. Rosa, Sadia Akter, Shibali Das, Mushtaq Ahmed, Maria de la Luz Garcia-Hernandez, Dhiraj K. Singh, Ekaterina Esaulova, Maxim N. Artyomov, Jennifer Gommerman, Smriti Mehra, Joaquin Zuniga, Makedonka Mitreva, Thomas J. Scriba, Javier Rangel-MorenoDeepak Kaushal, Shabaana A. Khader

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-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 TFH-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.

Original languageEnglish
Pages (from-to)855-868
Number of pages14
JournalNature immunology
Volume24
Issue number5
DOIs
StatePublished - May 2023

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