Marginal zone precursor B cells as cellular agents for type I IFN-promoted antigen transport in autoimmunity.
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 (BXD2-Ifnalphar(-/-)) 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-Ifnalphar(-/-) 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.
Wang
John H
JH
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Li
Jun
J
Wu
Qi
Q
Yang
PingAr
P
Pawar
Rahul D
RD
Xie
Shutao
S
Timares
Laura
L
Raman
Chander
C
Chaplin
David D
DD
Lu
Lu
L
Mountz
John D
JD
Hsu
Hui-Chen
HC
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*
D001324:Autoantigens; D007370:Interferon Type I