Stromal structure remodeling by B lymphocytes limits T cell activation in lymph nodes of Mycobacterium tuberculosis–infected mice
Lina Daniel, … , Warwick J. Britton, Carl G. Feng
Lina Daniel, … , Warwick J. Britton, Carl G. Feng
Published November 1, 2022
Citation Information: J Clin Invest. 2022;132(21):e157873. https://doi.org/10.1172/JCI157873.
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Research Article Immunology Infectious disease

Stromal structure remodeling by B lymphocytes limits T cell activation in lymph nodes of Mycobacterium tuberculosis–infected mice

Abstract

An effective adaptive immune response depends on the organized architecture of secondary lymphoid organs, including the lymph nodes (LNs). While the cellular composition and microanatomy of LNs under steady state are well defined, the impact of chronic tissue inflammation on the structure and function of draining LNs is incompletely understood. Here we showed that Mycobacterium tuberculosis infection remodeled LN architecture by increasing the number and paracortical translocation of B cells. The formation of paracortical B lymphocyte and CD35+ follicular dendritic cell clusters dispersed CCL21-producing fibroblastic reticular cells and segregated pathogen-containing myeloid cells from antigen-specific CD4+ T cells. Depletion of B cells restored the chemokine and lymphoid structure and reduced bacterial burdens in LNs of the chronically infected mice. Importantly, this remodeling process impaired activation of naive CD4+ T cells in response to mycobacterial and unrelated antigens during chronic tuberculosis infection. Our studies reveal a mechanism in the regulation of LN microanatomy during inflammation and identify B cells as a critical element limiting the T cell response to persistent intracellular infection in LNs.

Authors

Lina Daniel, Nayan D. Bhattacharyya, Claudio Counoupas, Yi Cai, Xinchun Chen, James A. Triccas, Warwick J. Britton, Carl G. Feng

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Figure 6

Chronic pulmonary M. tuberculosis infection impairs naive CD4+ T cell response to an unrelated antigen in mLN.

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Chronic pulmonary M. tuberculosis infection impairs naive CD4+ T cell re...
(A) Experimental design. B6 mice were infected with Ag85b–/– M. tuberculosis intranasally (i.n.) or remained uninfected. At 16 weeks p.i., infected and uninfected mice received i.v. CTV-labeled splenocytes from Ag85b-specific P25.CD45.1+.Rag1–/– TCR-Tg mice (~5 × 105 CD4+ T cells per recipient). Twenty-four hours later, both groups of mice were inoculated with 10 μg Ag85b240–254 peptide together with Pam2Cys adjuvant i.n. The mLNs were collected 48 hours after inoculation. (B and C) Flow cytometry plots showing the expression of CD69 on CTV-labeled P25 cells (B) and summary graph of the proportion of divided P25 cells (CTV low) (C) in mLN of uninfected (Un) and infected (Mtb) mice. (D) Representative flow cytometry plots showing the expression of CD62L, CD69, and CD25 on P25 cells. (E) Summary graphs showing the proportion of CD69+ and CD25+ P25 cells in mLN of uninfected and M. tuberculosis–infected mice. (F) The proportion of P25 cells in total CD4+ T cells in infected and uninfected mice. Data shown are from 2 independent experiments (n = 10 mice per group in total). Statistical differences between groups were determined using Student’s t test. *P < 0.05, ****P < 0.0001.