Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor.

Abstract

It has long been clear that there are two components of the B cell response to antigen. There is an early phase of proliferation in which the responding B cell population is expanded many times, and a later phase of differentiation in which the already proliferating B cell moves on to the immunoglobulin-secretion stage. It has been suggested that separate signals are involved in each phase (1); it has also been realized that there must be an initial lag phase (2) before the onset of proliferation; more recent studies (3) have defined this activation step as a separate event.It has been many years since the need for a helper T cell in the B cell response to antigen was defined (4, 5) and since the demonstration that the T cell could be replaced by a helper factor (6).It is now known that a number of T cell-and macrophage-derived nonantigenspecific factors make up the activity previously defined as "helper factor." Current studies are underway to characterize each factor and to determine at which stage it acts and what is its exact role. Parker (7) has shown that B cell proliferation can be seen in cultures of positively selected B cells stimulated with anti-#. He showed that anti-# alone was not sufficient, but that interleukin 2-(IL-2) 1 containing supernatants were also required. Immunoglobulin secretion required an additional factor (or factors) not provided in IL-2, but which were present in the supernatant of concanavalin A-(Con A) stimulated T cells. Howard et al. (8; and M. Howard, personal communication) also showed that a number of factors were required for B cell proliferation. In her analysis, the extent of proliferation to anti-Ig was proportional to the third power of the B cell concentration. The slope of this curve was reduced to two by the addition of an IL-2-containing supernatant from EL4 and to nearly one by the further addition of an 18-mol wt cut from the supernatant of P388D1 (presumably, interleukin 1 [IL-1]). The B cell growth factor (BCGF) activity present in the EL4 supernatants could be separated from the IL2 activity by phenyl Sepharose

Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation.

“…This difference is consistent with results obtained with both human and murine B cells and B-cell lines, which reproducibly demonstrate a lack of growth factor activity by (1,2,18,26). On the other hand, IL-5 can clearly stimulate the growth of human as well as mouse B cells (17,18,(35)(36)(37)(38). CH12 represents the first cell line, to our knowledge, in which the growth-inducing activity of these two factors could be assessed with a single clone of B cells that differentiate in response to both lymphokines.…”

“…IL-5 was originally described as a factor that induced both growth and differentiation of B cells (reviewed in references 37 and 38). IL-5 enhances the growth of B cells stimulated with dextran sulfate, but not with anti-immunoglobulin (anti-Ig) and IL4, and induces growth and differentiation of certain B-cell lymphomas, including BCL1 (28,34,35,37) and CH12 (21,31,36). IL-6 was originally described as a human B-cell differentiation factor that acts on activated, but not resting, B cells and certain B-cell leukemias (reviewed in references 17 and 41).…”

INTERLEUKIN-6: From Basic Science to Medicine—40 Years in Immunology

“…It is now called IL-4. The presence of a second BCGF activity was also reported by several groups, including K. Takatsu's and S. Swain's (25,26). This factor, which they called B151 TRF or (DL)BCGF, induced growth and IgM production in the murine B cell line, BCL 1 .…”

B cell dependence on and response to accessory signals in murine lupus strains.

“…Some authors have described production of BCGF (19), BCDFs (26), or TRF (28) by cloned T cell lines. Unfortunately, such T cell lines may produce several factors (19,29,30), and purified products are not yet available for study. For this reason, we have not at the present extended our study to analyze lymphokines derived from T cell lines.…”