Stromal structure remodeling by B lymphocytes limits T cell activation in lymph nodes of Mycobacterium tuberculosis–infected mice
Lina Daniel, Nayan D. Bhattacharyya, Claudio Counoupas, Yi Cai, Xinchun Chen, James A. Triccas, Warwick J. Britton, Carl G. Feng
Lina Daniel, Nayan D. Bhattacharyya, Claudio Counoupas, Yi Cai, Xinchun Chen, James A. Triccas, Warwick J. Britton, Carl G. Feng
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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 4

M. tuberculosis is mainly contained in CD11b+ myeloid cells within paracortical B cell clusters.

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M. tuberculosis is mainly contained in CD11b+ myeloid cells within para...
(A and B) Immunofluorescence images of mLN from naive and week 3 and 8 M. tuberculosis–infected mice stained for CD169 (A) (scale bars: 50 μm) and CD11b (B) (scale bars: 300 μm). Dashed white line delineates B cell follicles, and solid white line defines the medulla. (C) Representative immunofluorescence staining of CD11b+ myeloid cells and M. tuberculosis bacteria. Scale bars: 50 μm. (D) Quantification of CD11b+M. tuberculosis+ foci in the subcompartments of the mLN at weeks 3 and 8 after M. tuberculosis infection. The analysis was performed on stitched images of entire mLN, and subcompartments of the mLN were defined as indicated in Figure 2B, top panel. (E) Representative image of CD11b+M. tuberculosis+ foci localized within B cell cluster in the paracortex. Scale bar: 50 μm. (F) Quantification of CD11b+M. tuberculosis+ foci within B cell clusters in the paracortex of whole mLN sections at weeks 3 and 8 after M. tuberculosis infection. Circles and bars denote the individual mLN sections and group means, respectively. Data shown in D and F are pooled from 3 independent experiments (n = 7–9 mice in total). Statistical differences between groups were determined using 1-way ANOVA with Tukey’s multiple-comparison test (D) or Student’s t test (F). *P < 0.05, **P < 0.01, ****P < 0.0001.