Table 1.
Clinical and basic immunological characteristics of patients with Crohn’s disease.
Fig 1.
B-cells accumulate around granulomas in affected colon tissue in Crohn’s disease.
A, Representative images of colon biopsies with granulomas and non-granulomatous tissue in two patients with Crohn’s disease. B, Magnifications of granulomatous tissue from panel A.
Fig 2.
Composition of the blood B-cell compartment in patients with Crohn’s disease.
A. Schematic overview of peripheral B-cell subsets. B. Average numbers of blood B cell subsets of 21 patients affected with Crohn’s disease (black bars) and 28 healthy controls (light grey bars). C. Distribution of IgM, IgA and IgG within CD21low in patients and controls D. Total CD21low B cells in relation to disease duration. Statistical analyses were performed with the Mann-Whitney test or Spearman correlation; *, P<0.05; **, P<0.01.
Fig 3.
Replication history and SHM levels in IGHV genes of natural effector B cells.
A, Replication history of naïve and natural effector B cells as assessed using the KREC assay [25]. B, IGHV mutation frequencies in rearranged IGH genes of natural effector B cells in patients and controls (total numbers of sequences indicated between brackets). Grey dots represent unique sequences; red lines represent median values. C, Selection for replacement mutation in IGHV-CDR (red line) and IGHV-FR regions (blue lines) as determined with the BASELINe program [28, 29]. Solid lines represent patients; dashed lines represent healthy controls. Selection Strengths >0 indicate positive selection. D, IGH-CDR3 size distributions. All individual sizes are indicated as grey dots, red lines representing median values. The dashed line represents median values for centroblasts and centrocytes. Sorted cells were analyzed from patients 15, 16, 18 and 19. Controls were published previously [30, 31]. Statistical analysis was performed with the Mann-Whitney test; *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.
Fig 4.
IgA and IgG subclass analysis.
A, Schematic representation of the constant region of the human IGH locus. B, Distribution of IgA and IgG subclass use in switched transcripts of healthy controls and patients with Crohn’s disease. Total numbers of analyzed sequences are indicated in the middle of the plots. χ2 Test was performed to analyze differences in distributions. C, Combined IGHV mutation frequencies in IgA and IgG transcripts in patients and controls (total numbers of sequences indicated between brackets). Grey dots represent unique sequences; red lines represent median values. Statistical analysis was performed with the Mann-Whitney test; *, P<0.05; **, P<0.01; ***, P<0.001.
Fig 5.
Effects of infliximab on blood B-cell and CD21low compartment.
A, Blood B-cell compartments in patients under treatment with infliximab. B, Absolute total numbers of IgM, IgA and IgG with low CD21 expression in controls, patients and patients under treatment with infliximab. Bars represent mean values ±SEM. Statistical analysis was performed with the Mann-Whitney test; *, P<0.05; **, P<0.01; ***, P<0.001.