Antiimmunoglobulin-treated B cells respond to a B cell differentiation factor for IgG1.

We have determined whether B cells previously activated by anti-Ig (anti-Ig blasts) are responsive to lymphokines that induce isotype switching. Culture of anti-Ig blasts with a mixture of lymphokines, including BSF-1, resulted in marked secretion of IgM and IgG1, but not other IgG isotypes. The IgG1 response of anti-Ig blasts to lymphokines was 13-fold greater than was observed with splenic B cells. B cell blasts induced by 8-mercaptoguanosine or dextran sulfate did not secrete high levels of any IgG isotype in response to lymphokines alone. An mAb against BSF-1 suppressed the IgG1 response of anti-Ig blasts, but not the IgM response to lymphokines. These data suggest that anti-Ig-treated B cells respond to at least one of the effects of BSF-1.

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Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.

Journal of Experimental Medicine ◽

10.1084/jem.157.2.730 ◽

1983 ◽

Vol 157 (2) ◽

pp. 730-742 ◽

Cited By ~ 121

Author(s):

G J Prud'Homme ◽

C L Park ◽

T M Fieser ◽

R Kofler ◽

F J Dixon ◽

...

Keyword(s):

T Cells ◽

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Mouse Strain ◽

Interleukin 2 ◽

Lymphoid Cells ◽

B Cell Differentiation ◽

Differentiation Factor ◽

Cell Differentiation Factor

Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2-phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.

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B cell growth factors and B cell differentiation factor from human T hybridomas. Two distinct kinds of B cell growth factor and their synergism in B cell proliferation.

Journal of Experimental Medicine ◽

10.1084/jem.157.2.583 ◽

1983 ◽

Vol 157 (2) ◽

pp. 583-590 ◽

Cited By ~ 138

Author(s):

M Okada ◽

N Sakaguchi ◽

N Yoshimura ◽

H Hara ◽

K Shimizu ◽

...

Keyword(s):

Growth Factors ◽

Cell Differentiation ◽

B Cells ◽

Cell Growth ◽

B Cell ◽

Culture Supernatant ◽

B Cell Differentiation ◽

Differentiation Factor ◽

A Cells ◽

Cell Differentiation Factor

Human T hybridomas secreting B cell growth factors (BCGF) and B cell differentiation factor (BCDF) have been established. Hybrid clones 77-A, 94-C, and 98-F secreted BCGF that induced proliferation of anti-IgM-stimulated normal B cells. The culture supernatant from 77-A cells could also maintain continuous proliferation of colony-forming B cells, but the factor from 94-C could not. The addition of the supernatant from 94-C cells to that from 77-A cells, however, synergistically augmented the proliferation of colony-forming B cells, demonstrating the existence of two distinct kinds of BCGF and the synergism between them. These supernatants, however, showed no interleukin 2 (IL-2) or BCDF activity. A hybrid clone, 90-E, secreted BCDF. The culture supernatant induced Ig production in Cowan I-stimulated normal B cells or in a transformed B cell line, CESS. However, the supernatant had no BCGF or IL-2 activity. Anti-Ig-stimulated B cells, but not IL-2-dependent T cells, absorbed BCGF activity and CESS cells absorbed BCDF activity but not BCGF activity in the culture supernatants from T hybridomas. Taken collectively, the results demonstrated that IL-2, BCGF, and BCDF were different molecules and acceptors specific for the each molecule are present on the each target cell.

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The Effects of Interleukin 2, Gamma Interferon, and B Cell Differentiation Factor on the Differentiation of Human B Cells

The Molecular Basis of B-Cell Differentiation and Function ◽

10.1007/978-1-4684-7035-2_9 ◽

1986 ◽

pp. 59-62

Author(s):

N. Nakagawa ◽

T. Nakagawa ◽

D. J. Volkman ◽

H. Goldstein ◽

J. L. Ambrus ◽

...

Keyword(s):

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Interleukin 2 ◽

Gamma Interferon ◽

B Cell Differentiation ◽

Differentiation Factor ◽

Human B Cells ◽

Cell Differentiation Factor

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T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells.

Journal of Experimental Medicine ◽

10.1084/jem.155.3.734 ◽

1982 ◽

Vol 155 (3) ◽

pp. 734-748 ◽

Cited By ~ 282

Author(s):

P C Isakson ◽

E Puré ◽

E S Vitetta ◽

P H Krammer

Keyword(s):

Cell Differentiation ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cell Lines ◽

Interleukin 2 ◽

B Cell Differentiation ◽

Differentiation Factor ◽

T Cell Lines ◽

Cell Differentiation Factor

Culturing BALB/c B cells for 6 d at low cell density in the presence of lipopolysaccharide (LPS) results in the appearance of a small number of IgG plaque-forming cells (PFC). The addition of supernatants from concanavalin A (Con A)-induced alloreactive (AKR anti-B6) long-term T cell lines (PK 7.1.1a and 7.1.2) or a T cell hybridoma (FS7-6.18) to LPS-treated B cells resulted in a marked increase in IgG PFC (3--10-fold higher than in cultures treated with LPS alone. The number of induced IgG PFC was not affected by removing IgG-bearing cells on the fluorescence-activated cell sorter, indicating that T cell-derived B cell differentiation factor enhances isotype switching of sIgG- cells, rather than selecting and expanding pre-existing subpopulations of sIgG+ cells. We also investigated the subclass of IgG produced in the absence or presence of T cell factors and found that PK 7.1.1a, PK 7.1.2, and FS7-6.18 supernatants selectively increased IgG1 production. Several other T cell supernatants containing a variety of lymphokines had no effect, suggesting that PK 7.1.1a, PK 7.1.2, and FS7-6.18 lines produce factor(s) that can specifically enhance the recovery of IgG secreting cells in culture in the presence of LPS. These factors, which we have termed B cell differentiation factors, are different from interleukin 1, interleukin 2, T cell-replacing factor, colony-stimulating factor, macrophage-activating factor, and immune interferon. Our results suggest that soluble factors produced by T cell lines and hybridomas can markedly influence both the class and subclass of Ig produced by B cells.

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