Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells.
Bcl10 is an intracellular protein essential for nuclear factor (NF)-kappaB activation after lymphocyte antigen receptor stimulation. Using knockout mice, we show that absence of Bcl10 impeded conversion from transitional type 2 to mature follicular B cells and caused substantial decreases in marginal zone and B1 B cells. Bcl10-deficient B cells showed no excessive apoptosis. However, both Bcl10-deficient follicular and marginal zone B cells failed to proliferate normally, although Bcl10-deficient marginal zone B cells uniquely failed to activate NF-kappaB efficiently after stimulation with lipopolysaccharide. Bcl10-deficient marginal zone B cells did not capture antigens, and Bcl10-deficient (Bcl10-/-) mice failed to initiate humoral responses, leading to an inability to clear blood-borne bacteria. Thus, Bcl10 is essential for the development of all mature B cell subsets.
Xue
Liquan
L
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Morris
Stephan W
SW
Orihuela
Carlos
C
Tuomanen
Elaine
E
Cui
Xiaoli
X
Wen
Renren
R
Wang
Demin
D
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology; D013296:Streptococcus pneumoniae
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D002352:Carrier Proteins; D016328:NF-kappa B