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Published ahead of print on January 6, 2006, doi:10.1164/rccm.200504-594OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 751-758, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200504-594OC

Original Article

Cigarette Smoke–induced Emphysema

A Role for the B Cell?

Barry W. A. van der Strate, Dirkje S. Postma, Corry-Anke Brandsma, Barbro N. Melgert, Marjan A. Luinge, Marie Geerlings, Machteld N. Hylkema, Anke van den Berg, Wim Timens and Huib A. M. Kerstjens

Departments of Respiratory Medicine and Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands

Correspondence and requests for reprints should be addressed to Prof. Huib A. M. Kerstjens, M.D., Ph.D., Department of Respiratory Medicine, University Medical Center Groningen, Postbox 30.001, NL-9700-RB Groningen, The Netherlands. E-mail: h.a.m.kerstjens{at}int.umcg.nl

Rationale: Little is known about what drives the inflammatory reaction in the development of chronic obstructive lung disease. B cells have been found.

Objective: To study the involvement of B cells in the development of emphysema.

Methods: The presence of B-cell follicles and their interaction with other cells were investigated in lungs of patients with chronic obstructive pulmonary disease and of smoking mice. B cells were isolated from lymphoid follicles by laser microdissection and analyzed for the presence of immunoglobulin rearrangements and somatic mutations.

Main Results: Lymphoid follicles consisting of B cells and follicular dendritic cells with adjacent T cells were demonstrated both in the parenchyma and in bronchial walls of patients with emphysema. A clonal process was observed in all follicles and the presence of ongoing somatic mutations was observed in 75% of the follicles, indicating oligoclonal, antigen-specific proliferation. Similar lymphoid follicles were detected in mice that had developed pulmonary inflammation and progressive alveolar airspace enlargement after smoking. The increase in the number of B-cell follicles was progressive with time and correlated with the increase in mean linear intercept. Specific bacterial or viral nucleic acids could not be detected.

Conclusions: B-cell follicles with an oligoclonal, antigen-specific reaction were found in men and mice with emphysema. In mice, the development was progressive with time and correlated with the increase in airspace enlargement. We hypothesize that these B cells contribute to the inflammatory process and/or the development and perpetuation of emphysema by producing antibodies against either tobacco smoke residues or extracellular matrix components.

Key Words: autoimmunity • B cell • chronic obstructive pulmonary disease • emphysema • inflammation




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