Mechanisms governing B cell developmental defects in invariant chain-deficient mice.
Invariant chain (Ii)-deficient mice exhibit profound B cell defects that have remained poorly understood, because they could not be simply explained by impaired Ag presentation. We found that Ii deficiency induced cell autonomous defects of two distinct B cell lineages. The life span of mature follicular (FO) B cells was reduced, accounting for their markedly decreased frequency, whereas, in contrast, marginal zone (MZ) B cells accumulated. Other Ii-expressing lineages such as B1 B cells and dendritic cells were unaffected. Surprisingly, the life span of FO B cells was fully corrected in Ii/I-Abeta doubly deficient mice, revealing that Ii-free I-Abeta chains alter FO B cell survival. In contrast, the accumulation of MZ B cells was controlled by a separate mechanism independent of I-Abeta. Interestingly, in Ii-deficient mice lacking FO B cells, the MZ B cells invaded the FO zone, suggesting that intact follicules contribute to the retention of B cells in the MZ. These findings reveal unexpected consequences of Ii deficiency on the development and organization of B cell follicles.
Benlagha
Kamel
K
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Park
Se-Ho
SH
Guinamard
Rodolphe
R
Forestier
Claire
C
Karlsson
Lars
L
Chang
Cheong-Hee
CH
Bendelac
Albert
A
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000502:physiology; D000955:Antigens, T-Independent / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000502:physiology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte; D000955:Antigens, T-Independent; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; C045084:invariant chain