| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology and Immunology and
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
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-
, TNF-
, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01 HL071241, R01 AI50732, and P01 AI063537, Albert Einstein College of Medicine, Montefiore Medical Center, Center for AIDS Research P30 AI051519 (to J.C.), and a Seed Grant from the American Medical Association Foundation (to P.J.M.). P.J.M. was a trainee on National Institutes of Health T32 AI007506 and a student in the Albert Einstein College of Medicine Medical Scientist Training Program. This work constitutes partial fulfillment of the thesis requirements for P.J.M. in the Graduate Division of Medical Sciences at the Albert Einstein College of Medicine.
2 Address correspondence and reprint requests to Dr. John Chan, Albert Einstein College of Medicine, Forchheimer 406, 1300 Morris Park Avenue, Bronx, NY, 10461. E-mail address: jchan{at}aecom.yu.edu
3 Abbreviations used in this paper: TB, tuberculosis; GC, germinal center; PNA, peanut agglutinin; PPD, purified protein derivative.
This article has been cited by other articles:
|
|
 |
|
  S. D. Chakravarty, G. Zhu, M. C. Tsai, V. P. Mohan, S. Marino, D. E. Kirschner, L. Huang, J. Flynn, and J. Chan Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs Infect. Immun., March 1, 2008; 76(3): 916 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Maglione, J. Xu, A. Casadevall, and J. Chan Fc{gamma} Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection J. Immunol., March 1, 2008; 180(5): 3329 - 3338. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
