Figure 1.
Gene expression profiling of sorted tonsil B cell populations.
The heatmap shown represents the differential gene expression identified using- SAM in tonsil PC (TPC), tonsil naïve, pre-GC/germinal center founder (GCF), dark zone/germinal center (GC) and memory B cells. A total of 1858 genes are shown. 1690 are upregulated and 168 are downregulated. The majority of the gene signature is shared with tonsil PB (TPB).
Table 1.
TPC differentially expressed genes and comparative expression in TPB.
Figure 2.
Gene expression profiling of circulating SLE B cells populations demonstrating the differential gene expression in SLE PC compared with SLE naïve and memory B cells.
A. 780 genes are differentially expressed in SLE PC compared to SLE naive and memory B cells identified using SAM. 571 genes shown in the heatmap are upregulated and 209 genes are downregulated in SLE PC compared to SLE naïve and memory B cells. B. The genes differentially expressed in SLE PC were then compared gene by gene for corresponding expression in sorted tonsillar B cell populations.
Figure 3.
Unique gene expression pattern of HLA class II genes in SLE PC in comparison to tonsil PC and PB.
Expression of HLA Class II genes in SLE PC, tonsil PC and tonsil PB. Differences in gene expression are shown as mean expression value log2 transformed data. Significance determined by student's t-test is denoted by asterisk(s) in the figure. Correction for multiple comparisons performed using Bonferroni correction.
Figure 4.
Relative expression of genes involved in lymphocyte trafficking.
S1P1, CD69 and CXCR4 were examined for gene expression in IgSC populations (tonsil PC and SLE PC). A significant difference (p<0.06) in gene expression among the populations is denoted in the figure and was determined by a student's t-test with a correction for multiple comparisons using Bonferroni correction.
Table 2.
Differentially expressed genes in SLE PC compared to tonsil Ig secreting cells.
Figure 5.
Comparative expression of bone marrow PC discriminating genes in SLE PC and tonsil PC.
51 genes previously reported to discriminate bone marrow PC from tonsil PC (A) were compared to gene expression profiles of SLE PC and tonsil PC from the current data set (B). The blue line in the figure divides the 51 genes into those that are similarly (top) and dissimilarly (bottom) expressed by SLE PC and bone marrow PC. Twenty-seven genes demonstrate a similar pattern of expression in SLE PC and bone marrow PC and 24 genes exhibit a dissimilar pattern of expression in bone marrow and SLE PC.
Figure 6.
The IFN signature in SLE B cell subpopulations.
A. A total of 54 genes identified using SAM are differentially expressed in SLE naïve and memory B cells compared with normal comparators. Fifty-three of the 54 genes are upregulated and 23 (denoted by an asterisk) comprise the IFN inducible gene signature. B. The expression of the genes shown in part A was assessed for corresponding expression in IgSC populations.
Figure 7.
Proposed plasma cell trafficking in SLE based on gene expression profiling.
Normal B cell traffic into germinal center reactions appears unchanged in SLE from normal. Plasma cells in SLE differ from tonsil plasma cells in expression of cell surface markers that may affect plasma cell homing to bone marrow. Plasma cells continue to mature in the blood and have a gene program upregulated similar to bone marrow plasma cells with long-lived potential. Downregulated gene program include continued and more pronounced decrease in expression of CXCR4, MHC class II and cell surface markers. Endogenous factors such as IFNα in SLE may contribute to these changes.