XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development.
The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1(fl/fl) CD19(+/cre) conditional knockout (XBP1(CD19)) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1(CD19) mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1(CD19) mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment.
Todd
Derrick J
DJ
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
McHeyzer-Williams
Louise J
LJ
Kowal
Czeslawa
C
Lee
Ann-Hwee
AH
Volpe
Bruce T
BT
Diamond
Betty
B
McHeyzer-Williams
Michael G
MG
Glimcher
Laurie H
LH
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology*; D000071701:Regulatory Factor X Transcription Factors; D053668:Syndecan-1 / Q000032:analysis; D014157:Transcription Factors / Q000502:physiology*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse