Recombinant human interleukin 6 (B cell stimulatory factor 2) enhances immunoglobulin secretion by single murine hapten-specific B cells in the absence of cell division.
We have assessed the role of recombinant human IL-6 (r-hu-IL-6) in promotion of early activation, proliferation, and immunoglobulin (Ig) secretion amongst single hapten-specific murine splenic B cells in vitro. It was found that r-hu-IL-6 acting alone was able to induce early B cell activation in a proportion of B cells, as measured by a significant increase in cell diameter within 24 h. An enhanced effect was seen in the concomitant presence of a 'T-independent' antigen. None of the B cells activated by r-hu-IL-6 appeared to divide, as the frequencies of proliferating clones induced by either medium alone or antigen alone were virtually identical whether r-hu-IL-6 was present or absent. However, assay of the culture supernatants for the presence of Ig by ELISA revealed that r-hu-IL-6 effected a significant 2-fold increase in the frequency of B cells secreting Ig. Thus, the prime effect of r-hu-IL-6 appears to be to recruit more precursor B cells into Ig secretion, rather than to promote proliferation or to enhance the amount of Ig secreted by pre-committed but non-cycling B cells. Delayed addition experiments showed that r-hu-IL-6 enhanced Ig secretion late in the activation pathway. Kinetics studies demonstrated detectable Ig secretion as early as day 2, and when taken with its apparent ability to induce early activation, these findings suggest that IL-6 is not exclusively a late-acting interleukin. Studies with size fractionated hapten-specific B cells showed the larger B cells to be preferentially responsive to r-hu-IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Alderson
M R
MR
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Pike
B L
BL
D000818:Animals; D000941:Antigens; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D006241:Haptens; D007136:Immunoglobulins / Q000378:metabolism*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA
D000941:Antigens; D006241:Haptens; D007136:Immunoglobulins; D015850:Interleukin-6; D015847:Interleukin-4