B cells in chronic obstructive pulmonary disease: moving to center stage

Abstract

Chronic inflammatory responses in the lungs contribute to the development and progression of chronic obstructive pulmonary disease (COPD). Although research studies focused initially on the contributions of the innate immune system to the pathogenesis of COPD, more recent studies have implicated adaptive immune responses in COPD. In particular, studies have demonstrated increases in B cell counts and increases in the number and size of B cell-rich lymphoid follicles in COPD lungs that correlate directly with COPD severity. There are also increases in lung levels of mediators that promote B cell maturation, activation, and survival in COPD patients. B cell products such as autoantibodies directed against lung cells, components of cells, and extracellular matrix proteins are also present in COPD lungs. These autoantibodies may contribute to lung inflammation and injury in COPD patients, in part, by forming immune complexes that activate complement components. Studies of B cell-deficient mice and human COPD patients have linked B cells most strongly to the emphysema phenotype. However, B cells have protective activities during acute exacerbations of COPD by promoting adaptive immune responses that contribute to host defense against pathogens. This review outlines the evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD and the mechanisms involved. It also reviews the potential and limitations of B cells as therapeutic targets to slow the progression of human COPD.

Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease

“…In addition, B cells, in particular B cell rich lymphoid follicles, are increased in the severe stages of COPD and are most strongly linked with the emphysematous changes in the lung (reviewed in Ref. ). Autoantibodies are also evident in the blood and lung samples from COPD patients .…”

MAP3K19 Is Overexpressed in COPD and Is a Central Mediator of Cigarette Smoke-Induced Pulmonary Inflammation and Lower Airway Destruction

“…Lung histological sections, stained with CD45/B220 showed the presence of lymphoid follicles in all cigarette smoke exposed cohorts, but not in air treated animals (S5 and S6 Figs). Lymphoid follicles, consisting of predominantly B lymphocytes, have been characterized in the lungs of patients with severe COPD [40, 41], and independently demonstrated that the chronic cigarette smoke exposure had a profound effect on the mice. Further examination of histological sections revealed airspace enlargement, as measured by mean linear intercept analysis, was greatest in the CS + vehicle and dexamethasone treated mice compared to the MAP3K19 inhibitor treated or air treated mice (Figs 9C and 10, S7 Fig).…”

Integrated transcriptomic correlation network analysis identifies COPD molecular determinants

“…Neutrophils provide powerful proteases and are most prominent in acute exacerbations in the lung airways [Tuder 2012]. The role of T and B cells in COPD pathogenesis has growing support from the basic science studies of COPD [Hogg 2004, Seys 2015, Polverino 2016, Morrow 2017. In fact, recent evidence shows a strong correlation between increases in the number and size of B cell-rich lymphoid follicles and COPD severity, as well as a strong correlation between T cell numbers and the amount of alveolar destruction and severity of airflow obstruction [Barnes 2016, Polverino 2016.…”

“…In fact, recent evidence shows a strong correlation between increases in the number and size of B cell-rich lymphoid follicles and COPD severity, as well as a strong correlation between T cell numbers and the amount of alveolar destruction and severity of airflow obstruction [Barnes 2016, Polverino 2016. Finally, B cell products (autoantibodies) were found in COPD blood and lung samples [Polverino 2016].…”