Figure 4
Figure 4. CXCL13 induces chemotaxis of CLL B cells, but not of multiple myeloma cells. CLL cell chemotaxis is pertussis-toxin sensitive and wortmannin sensitive. (A) CLL cell chemotaxis was measured toward increasing concentrations of CXCL13, and/or 100 ng/mL CXCL12, as indicated on the horizontal axis. The bars represent relative proportion of input CLL cells that had migrated within 2 hours in response to the chemokine(s), as indicated on the vertical axis, and are the mean (± SD) from 16 different patients. (B) In contrast to CLL B cells from a representative patient (▄), multiple myeloma cells from 2 different patients ( and ) did not display chemotaxis to the different concentrations of CXCL13 that are indicated on the horizontal axis. However, myeloma cells from one patient (MM no. 2) displayed robust chemotaxis to 100 ng/mL CXCL12. (C) To determine signaling pathways involved in CLL cell chemotaxis to CXCL13, CLL cells were preincubated with the reagents that are displayed on the vertical axis before being assayed for chemotaxis to 1000 ng/mL CXCL13. The bars depict the mean (± SEM) relative chemotaxis of CLL cells from 8 different patients after treatment with the various agents compared with untreated controls (100%). Anti-CXCR5 mAbs, wortmannin, and pertussis toxin significantly inhibited CLL cell chemotaxis to CXCL13, as indicated by the asterisks.

CXCL13 induces chemotaxis of CLL B cells, but not of multiple myeloma cells. CLL cell chemotaxis is pertussis-toxin sensitive and wortmannin sensitive. (A) CLL cell chemotaxis was measured toward increasing concentrations of CXCL13, and/or 100 ng/mL CXCL12, as indicated on the horizontal axis. The bars represent relative proportion of input CLL cells that had migrated within 2 hours in response to the chemokine(s), as indicated on the vertical axis, and are the mean (± SD) from 16 different patients. (B) In contrast to CLL B cells from a representative patient (▄), multiple myeloma cells from 2 different patients ( and ) did not display chemotaxis to the different concentrations of CXCL13 that are indicated on the horizontal axis. However, myeloma cells from one patient (MM no. 2) displayed robust chemotaxis to 100 ng/mL CXCL12. (C) To determine signaling pathways involved in CLL cell chemotaxis to CXCL13, CLL cells were preincubated with the reagents that are displayed on the vertical axis before being assayed for chemotaxis to 1000 ng/mL CXCL13. The bars depict the mean (± SEM) relative chemotaxis of CLL cells from 8 different patients after treatment with the various agents compared with untreated controls (100%). Anti-CXCR5 mAbs, wortmannin, and pertussis toxin significantly inhibited CLL cell chemotaxis to CXCL13, as indicated by the asterisks.

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