Cigarette smoke-induced emphysema: A role for the B cell?
BACKGROUND
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.


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.
van der Strate
Barry W A
BW
Department of Respiratory Medicine, University Medical Center Groningen, Postbox 30.001, NL-9700-RB Groningen, The Netherlands.
Postma
Dirkje S
DS
Brandsma
Corry-Anke
CA
Melgert
Barbro N
BN
Luinge
Marjan A
MA
Geerlings
Marie
M
Hylkema
Machteld N
MN
van den Berg
Anke
A
Timens
Wim
W
Kerstjens
Huib A M
HA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D004247:DNA