Heterogeneity of B cell responsiveness to interleukin 4, interleukin 6 and low molecular weight B cell growth factor in discrete stages of B cell activation in patients with systemic lupus erythematosus.

To investigate the differential stages of B cell activation in patients with systemic lupus erythematosus (SLE), the effects of recombinant interleukin-4 (rIL-4) interleukin-6 (rIL-6), and low mol. wt BCGF (1-BCGF) on B cell proliferation and differentiation were evaluated. In a co-stimulatory assay with anti-IgM, proliferative response to rIL-4 and 1-BCGF showed no significant differences between SLE patients and healthy controls. In a restimulation assay, after pre-activation with anti-IgM for 3 days, proliferative response to rIL-4 and 1-BCGF was significantly decreased in SLE patients compared with normal healthy controls (P less than 0.01). With regard to rIL-6 induced B cell differentiation, SAC-pre-activated low density, large B cells from both SLE patients and healthy controls differentiated well, whereas high density B cells did not differentiate at all. Of particular interest, low density B cells from active patients directly differentiated into Ig secreting cells in response to rIL-6 without SAC activation. These data indicate that heterogeneity of B cell responsiveness to B cell-tropic interleukins resulted from the discrete stages of B cell activation in SLE.