期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 1, 页码 442-451出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0900870
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资金
- American College of Rheumatology Research and Education Foundation
- Department of Veterans Affairs Merit Review [1101BX000600-01]
- Daiichi-Sankyo
- National Institutes of Health [IA1 071110-01A1, ARRA 3RO1A171110-02S1]
- The University of Alabama at Birmingham Skin Diseases Research Center
- Arthritis Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI076562, R01AI071110] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P30AR048311, P30AR050948] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX000600] Funding Source: NIH RePORTER
The pathogenic connection of type I IFN and its role in regulating the migration response of Ag delivery by B cells into lymphoid follicles in an autoimmune condition has not been well-identified. Here, we show that there was a significantly larger population of marginal zone precursor (MZ-P) B cells, defined as being IgM(hi)CD1d(hi)CD21(hi)CD23(hi) in the spleens of autoimmune BXD2 mice compared with B6 mice. MZ-P B cells were highly proliferative compared with marginal zone (MZ) and follicular (FO) B cells. The intrafollicular accumulation of MZ-P B cells in proximity to germinal centers (GCs) in BXD2 mice facilitated rapid Ag delivery to the GC area, whereas Ag-carrying MZ B cells, residing predominantly in the periphery, had a lower ability to carry Ag into the GCs. IFN-alpha, generated by plasmacytoid dendritic cells, induced the expression of CD69 and suppressed the sphingosine-1-phosphate-induced chemotactic response, promoting FO-oriented Ag transport by MZ-P B cells. Knockout of type I IFN receptor in BXD2 (MID2-Ifn alpha r(-/-)) mice substantially diffused the intrafollicular MZ-P B cell conglomeration and shifted their location to the FO-MZ border near the marginal sinus, making Ag delivery to the FO interior less efficient. The development of spontaneous GCs was decreased in BXD2-Ifn alpha r(-/-) mice. Together, our results suggest that the MZ-P B cells are major Ag-delivery B cells and that the FO entry of these B cells is highly regulated by type I IFN-producing plasmacytoid dendritic cells in the marginal sinus in the spleens of autoimmune BXD2 mice. The Journal of Immunology, 2010, 184: 442-451.
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