Age-associated B Cells Appear in Patients with Granulomatous Lung Diseases

Abstract

Rationale: A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients.Objectives: To measure ABC-like cell percentages in patients with lung granulomatous diseases.Methods: Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet.Measurements and Main Results: ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood.Conclusions: Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.

Prevalence and characteristics of self-reported hypothyroidism and its association with nonorgan-specific manifestations in US sarcoidosis patients: a nationwide registry study

“…Additionally, the increase in circulating immunoglobulins and the possible response to Bcells depleting therapy in refractory cases might suggest a role of humoral immune system as well [26]. Recently, sarcoidosis patients were found to have elevated levels of age associated B-cells in their blood and bronchoalveolar lavage as compared to healthy subjects supporting the role of B-cell immunity [27]. This autoimmune phenomenon in sarcoidosis might explain the higher prevalence of hypothyroidism noted in our sarcoidosis cohort as compared to the general population.…”

Clinical Presentations, Pathogenesis, and Therapy of Sarcoidosis: State of the Art

“…Case-report evidence of responses to rituximab exists in extrapulmonary sarcoidosis but not for pulmonary disease as yet [71]. Recently, age-associated B cells (ABCs) [72], B cell subtypes associated with aging, in which they contribute to inflammation [73], have been found increased in peripheral blood and BAL (relative to healthy subjects) in patients with sarcoidosis [74] but their role needs to be clarified.…”

The ABCs of Granulomatous Lung Diseases: Age-associated B Cells

“…Third, regardless of participant disease status, ABC-like cells expressed less FcRL1 and more FcRL2, 3, 4, and 5 relative to non-ABC–like B cells (“other B cells”). Fourth, besides defining correlations between individual receptors compatible with coregulation, they surprisingly found no significant difference in percentages of BAL ABC-like cells between individuals with BeS versus established CBD ( 23 ).…”

“…In this issue of the Journal , Phalke and colleagues (pp. 1013–1023 ) ( 23 ) from the laboratory of the renowned immunologist Philippa Marrack extend their seminal work on ABCs ( 21 , 24 – 27 ). Acknowledging the nomenclature controversies ( 19 , 28 , 29 ) by referring to them as “ABC-like cells,” they present several novel, interesting findings.…”

“…Because circulating ABCs are increased in multiple diseases and in aging, their utility to make any specific diagnosis is limited ( 30 ). Nevertheless, combining the equivalent percentages of BAL ABC in BeS and CBD ( 23 ) with the protective role of conventional B cells in a transgenic model of CBD ( 13 ) suggests an intriguing possibility. ABCs may be recruited by granulomatous inflammation without an essential role in initiating pathology, but once there, responding to local IL-21 ( 31 , 32 ), their T-bet+ clones in particular ( 20 ) might drive T-cell responses.…”