Lymphoid follicles in (very) severe COPD: beneficial or harmful?

Abstract

Inflammation is a main pathogenetic factor in the development and progression of chronic obstructive pulmonary disease (COPD). Recently, it has become clear that not only the innate, but also the specific immune response plays a role. A striking finding, in particular in lungs of patients with severe COPD, often with a predominant emphysema phenotype, is the presence of B-cell follicles. As seen in other tissues, these follicles are the result of lymphoid neogenesis. The finding of oligoclonality in B-cell follicles in COPD suggests that they play a role in local antigen specific immune responses. To date, it is not known which antigens may be involved; microbial antigens, cigarette smoke-derived antigens and antigens from extracellular matrix breakdown products have been suggested. Consequently, the pathogenetic role of this follicular B-cell response is not yet clear. It might be protective against microbial colonisation and infection of the lower respiratory tract and, therefore, beneficial, or it could be of a more harmful (autoimmune) nature, directed against lung tissue components. It is necessary to determine the specific antigen(s) and to explore the exact role of the COPD related B-cell response in order to include modulation of this response and develop therapeutic options.

CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice

“…Pulmonary lymphoid follicles may be harmful by sustaining immune responses and subsequent chronic inflammation (reviewed in Ref. 35) or protective against bacterial and viral infection (36). Notably, the CCL19-CCL21-CCR7 axis appears important for the function of pulmonary lymphoid tissue, and blockade at this level has been shown to negatively affect adaptive immune responses against respiratory pathogens (13).…”

Significant increase of CD57+ cells in pulmonary lymphoid follicles of COPD patients

“…Recently, this inflammatory process has been associated with the development of ectopic lymphoid follicles (LFs) in lungs of COPD patients [2][3][4][5][6][7], which are similar to the tertiary lymphoid tissue found in other inflammatory or autoimmune diseases [8,9].…”

Small Airways Disease in Chronic Obstructive Pulmonary Disease: A 50 Years History

“…Further independent studies of tertiary lymphoid organs located in alveolar tissue in COPD 28,29 , have also shown that these lymphoid follicles contain both memory and Moreover, the presence of these tertiary lymphoid organs provides definitive support for the presence of an adaptive immune response in the later stages of COPD. Furthermore, the observations that the B cell activating factor (BAFF), and lymphotoxin (TNF-LT) that are both members of the tumour necrosis factor (TNF) super family are upregulated in COPD implicated their role in regulating the development and maintenance of lymphoid follicles in COPD 30 .…”

“…These findings strongly support the hypothesis that B cells in tertiary lymphoid organs are responding to antigens in COPD. Even though they provide no information about the antigens that are driving this response 29 .…”