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Published ahead of print on January 6, 2006, doi:10.1164/rccm.200504-594OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 7, April 2006, 751-758

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Submitted on April 17, 2005
Accepted on January 6, 2006

Cigarette Smoke-induced Emphysema: A Role for the B Cell?

Barry W.A. van der Strate1, Dirkje S Postma2, Corry-Anke Brandsma1, Barbro N Melgert1, Marjan A Luinge1, Marie Geerlings1, Machteld N Hylkema3, Anke van den Berg3, Wim Timens3, and Huib A.M. Kerstjens2*

1 Department of Respiratory Medicine, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands, 2 Department of Respiratory Medicine, University Medical Center Groningen, Groningen, The Netherlands, 3 Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands

* To whom correspondence should be addressed. 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 recently 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 was investigated in lungs of patients with COPD 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: COPD, emphysma, B-cell, auto-immunity, inflammation




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