B cells moderate inflammatory progression and enhance bacterial containment upon pulmonary challenge with Mycobacterium tuberculosis

J Immunol. 2007 Jun 1;178(11):7222-34. doi: 10.4049/jimmunol.178.11.7222.

Abstract

Though much is known about the function of T lymphocytes in the adaptive immune response against Mycobacterium tuberculosis, comparably little is understood regarding the corresponding role of B lymphocytes. Indicating B cells as components of lymphoid neogenesis during pulmonary tuberculosis, we have identified ectopic germinal centers (GCs) in the lungs of infected mice. B cells in these pulmonary lymphoid aggregates express peanut agglutinin and GL7, two markers of GC B cells, as well as CXCR5, and migrate in response to the lymphoid-associated chemokine CXCL13 ex vivo. CXCL13 is negatively regulated by the presence of B cells, as its production is elevated in lungs of B cell-deficient (B cell(-/-)) mice. Upon aerosol with 100 CFU of M. tuberculosis Erdman, B cell(-/-) mice have exacerbated immunopathology corresponding with elevated pulmonary recruitment of neutrophils. Infected B cell(-/-) mice show increased production of IL-10 in the lungs, whereas IFN-gamma, TNF-alpha, and IL-10R remain unchanged from wild type. B cell(-/-) mice have enhanced susceptibility to infection when aerogenically challenged with 300 CFU of M. tuberculosis corresponding with elevated bacterial burden in the lungs but not in the spleen or liver. Adoptive transfer of B cells complements the phenotypes of B cell(-/-) mice, confirming a role for B cells in both modulation of the host response and optimal containment of the tubercle bacillus. As components of ectopic GCs, moderators of inflammatory progression, and enhancers of local immunity against bacterial challenge, B cells may have a greater role in the host defense against M. tuberculosis than previously thought.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / microbiology*
  • B-Lymphocyte Subsets / transplantation
  • Cells, Cultured
  • Chemokine CXCL13
  • Chemokines, CXC / antagonists & inhibitors
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / physiology
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology
  • Disease Progression
  • Female
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Granuloma, Respiratory Tract / genetics
  • Granuloma, Respiratory Tract / immunology
  • Granuloma, Respiratory Tract / microbiology
  • Granuloma, Respiratory Tract / pathology
  • Lung / immunology*
  • Lung / microbiology
  • Lung / pathology*
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Lymphopenia / microbiology
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CXCR5
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / physiology
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology*
  • Tuberculosis, Pulmonary / pathology*

Substances

  • CXCR5 protein, mouse
  • Chemokine CXCL13
  • Chemokines, CXC
  • Cxcl13 protein, mouse
  • Receptors, CXCR5
  • Receptors, Chemokine