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.
View: Text | PDF
Research Article Immunology Infectious disease Article has an altmetric score of 36

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

×

Figure 2

B cell expansion disturbs stromal cell organization in M. tuberculosis–infected mLN.

Options: View larger image (or click on image) Download as PowerPoint
B cell expansion disturbs stromal cell organization in M. tuberculosis–i...
(A) Images of mLN sections from naive and infected mice. Dashed line delineates the B cell follicles (staining not shown). Scale bars: 300 μm. (B) Representative image of B220- and CD3-stained week 8 M. tuberculosis–infected mLN. Scale bar: 300 μm. Boxed area represents the cortex-medullary axis. Scale bar: 50 μm. The histograms represent the average fluorescence intensity of each marker along the cortex/medullary axis of the mLN. Dashed line: boundary between the follicles, paracortex, and medulla. (C) Ifng and Ccl21 expression in uninfected and 8-week-infected LNs measured by qRT-PCR. Data are the mean fold increase (n = 4) ± SD relative to nondraining inguinal LN. (D) mLN images of 8-week M. tuberculosis–infected chimeric mice (WT or Ifngr–/– recipients reconstituted with WT bone marrow cells). White line: paracortical B cell cluster boundary. Scale bars: 50 μm. (E) Images of B220-, CD3-, and PDPN-stained mLN from naive and 8-week M. tuberculosis–infected mice. White line: paracortical B cell cluster boundary. Scale bars: 50 μm. (F) mLN sections from naive and 8-week M. tuberculosis–infected mice. Arrowheads indicate CD35+ FDC-containing paracortical B cell clusters in infected mLN. Expression of B220, CD3, or CD35 in a paracortical B cell cluster (boxed region) in M. tuberculosis–infected mLN is shown at right. Scale bars: 100 μm (left) and 50 μm (right). (G) Quantification of paracortical B cell clusters with or without CD35+ cells in infected mLN. Data in A, B, and D–F are representative of 2 independent experiments with similar results (n = 4 mice per group), and data in G are from 2 experiments (n = 6 mice). Statistical differences between groups were determined using Student’s t test. *P < 0.05, ****P < 0.0001. M.tb, M. tuberculosis.