The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells.

Abstract

The role of recombinant B cell stimulatory factor 2 (BSF-2/IL-6) in the regulation of growth and differentiation of B cells was investigated. rBSF-2 at 200 pg/ml could induce 50% of the maximum Ig production in B lymphoblastoid cell lines, the specific activity being estimated as 5 X 10(6) U/mg. rBSF-2 augmented PWM-induced IgM, IgG, and IgA production in mononuclear cells (MNC); the effect was exerted by directly acting on PWM-induced B blast cells to induce Ig production. However, rBSF-2 did not induce any growth of activated B cells. In contrast, rBSF-2 showed a potent growth activity on a murine hybridoma clone, MH60.BSF2. The concentration required for half-maximal [3H]TdR uptake was approximately 5 pg/ml, which was 40 times less than that required for Ig induction in a B cell line. Anti-BSF-2 antibody inhibited PWM-induced Ig production in MNC, but not PWM-induced proliferation. The antibody was effective even when added on day 4 of an 8-d culture, indicating that BSF-2 is one of the essential late-acting factors in PWM-induced Ig production.

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

“…These results are consistent with in vitro studies in which IL-6 was shown to be an important B cell differentiation factor for the development of immunoglobulin-secreting cells (5,39). Culturing B cells in vitro with anti-IL-6 antibodies inhibited immunoglobulin production even when added on the fourth day of an 8-day culture, indicating that IL-6 acts on the late phase of the B cell response (5). Interestingly, a marked reduction of mucosal IgA-producing cells has been observed, along with deficient local antibody responses in IL-6-deficient mice (40).…”

“…It is important to note that all serum immunoglobulin levels stayed within in the normal range and did not drop below the lower limit of normal. These results are consistent with in vitro studies in which IL-6 was shown to be an important B cell differentiation factor for the development of immunoglobulin-secreting cells (5,39). Culturing B cells in vitro with anti-IL-6 antibodies inhibited immunoglobulin production even when added on the fourth day of an 8-day culture, indicating that IL-6 acts on the late phase of the B cell response (5).…”

“…antibody-producing plasma cells (5). Excessive activity of IL-6 causes polyclonal B cell activation, plasmacytosis, and B cell neoplasia.…”

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

“…However, in most IL-6 KO mouse groups, there were significant decreases in the IgG2a responses as compared with WT mice. Since there were no accompanied reductions of IFN-γ responses, the effect may be a result of the lack of direct interaction of IL-6 on B cells [24,46], and/or via the activities of DCs [47]. Of further interest is the lack of reduction of IgG2a responses in IL-6 KO mice receiving adjuvant formulations containing QS21, ie.…”

Targeting Interleukin-6 in Rheumatoid Arthritis

“…IL-6 stimulates B cells to differentiate into plasma cells which produce immunoglobulin [12]. It also influences T-cell development by stimulating the proliferation and differentiation of T lymphocytes into TH-17 cells which produce IL-17.…”