Deficiency of regulatory B cells increases allergic airway inflammation.
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 IFNgamma 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.
Lundy
S K
SK
Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, 48109, USA.
Berlin
A A
AA
Martens
T F
TF
Lukacs
N W
NW
D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018956:CD5 Antigens / Q000032:analysis; D018946:Chemokine CCL5 / Q000378:metabolism; D003058:Cockroaches / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism
D015704:CD4 Antigens; D018956:CD5 Antigens; D018946:Chemokine CCL5; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D007073:Immunoglobulin E