Deficiency of regulatory B cells increases allergic airway inflammation

Abstract

Objective-To investigate the effect of the X-linked immunodeficiency (Xid) B cell defect on the response to the cockroach allergen in mice.Methods-Two cockroach allergen immunization and challenge protocols were employed to sensitize CBA/J wild-type and CBA/CaHN-btk(−/−)xid/J (Xid) mice. Blood and tissue samples were collected 24 and 48 hrs after the last intratracheal antigen challenge and were analyzed for several parameters of allergic inflammation.Results-Nearly equivalent amounts of serum IgE were detected in Xid and CBA/J mice after short-term antigen challenge despite the B cell deficiency in Xid mice. A decreased concentration of IgE was detected in CBA/J mice after repeated allergen challenges but not in the Xid mice. Correlating with the discrepancy in serum IgE levels, higher levels of IL-13, IL-5, IL-10 and CCL5 were measured in whole lung homogenates from allergen-challenged Xid mice compared to CBA/J mice. In addition, draining lymph node cells from Xid mice expressed elevated levels of IL-4, IL-5, IL-10 and IFNγ mRNA compared to cells from CBA/J mice after in vitro culture with cockroach antigen. An increase in lung inflammation, interstitial eosinophilia and mucus production was also observed in allergen-challenged Xid mice. CD95L expression increased on B-1a cells following allergen challenge, which was accompanied by an increase in lung CD4 + Th cell apoptosis in wild-type CBA/J mice. In contrast, Xid mice did not have an increase in CD4 + T cell apoptosis following allergen challenge.Conclusions-These data suggest a regulatory role for B-1a cells in reducing cytokine production, pulmonary inflammation, and CD4 + T cell survival during cockroach allergen-induced airway inflammation.

Regulatory Role of B Cells in a Murine Model of Allergic Airway Disease

“…Despite resolution of the airway eosinophilia, we have observed persistent expansion of T and B lymphocytes in bronchoalveolar lavage (BAL) fluid and regional hilar lymph nodes (HLN) from mice with LIT (2,3). Other investigators have implicated putative Breg cells in the development of nasal tolerance to aeroallergens (20) and in the suppression of AAD (21). Therefore, the purpose of this study was to investigate the role of B cells in the resolution of AAD and induction of LIT in this OVA model.…”

Induction of CD4+ T-cell anergy and apoptosis by activated human B cells

“…10,11 This was first demonstrated in respective mouse models, where absence of B cells led to an exacerbated course of diseases such as autoimmune encephalomyelitis, chronic colitis, schistosoma infection, and allergy. [12][13][14][15] Further research revealed different potential mechanisms, among them signaling via Fc␥R, 13,14 down-regulation of Th1 response, 16,17 production of immunosuppressive cytokines, [18][19][20][21] and induction of Tregs. 22,23 Unfortunately in many of these in vivo mouse models, "thirdparty" effects, for example, via dendritic cells could not always be excluded.…”

B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

“…B-cell antigen presentation is becoming increasingly recognized as an important contributor to disease pathogenesis. 4,[48][49][50] Previous studies using mMT mice in an asthma model have suggested that B cells help to mediate Th2 responses. Using a cockroach antigen model, Lindell et al 4 reported a 50% decrease in Th2 cytokines in the absence of B lymphocytes.…”

“…B cells might have a regulatory role in allergic asthma 4,50,51 or indirectly influence the T-cell response through the alteration of DC function and/or lymph node organization, modifying the resulting phenotype of the response. 48,49,52 In the current study, we demonstrate an expanded role for B lymphocytes in regulating inflammation in the allergic lung.…”