title: Differential induction of class II gene expression in murine pre-B-cell lines by B-cell stimulatory factor-1 and by antibodies to B-cell surface antigens.
abstract: We have previously reported that BSF-1 and an alloantibody to the B-cell differentiation antigen Lyb2 induce class II gene expression in two Ia negative pre-B-cell lines. Two questions were asked in these studies. The first question is whether the different stimuli which we and others have shown to induce class II expression in B-cells act via the same signal transduction mechanisms. The second question is whether the traditionally accepted pathway of B-cell differentiation, as defined by immunoglobulin (Ig) gene rearrangement, is applicable to other events that occur during B-cell differentiation. In this report, we have therefore examined a large panel of pre-B-cell lines at different stages of Ig gene rearrangement in an attempt to 1) identify the stage in B-cell development where class II gene expression occurs and where it becomes inducible by BSF-1 or anti-Lyb2, and 2) compare the signal transduction mechanisms used by these ligands. The majority of pre-B-cell lines tested did not express BSF-1 receptors and were consequently noninducible for class II by BSF-1; such cell lines were, however, inducible for class II expression by anti-Lyb2 and, in addition, by antibodies to the B220 membrane glycoprotein. The induction of class II molecules by BSF-1 and by anti-Lyb2 and anti-B220 differed in several respects: 1) Induction by anti-Lyb2 and anti-B220 did not require the presence of BSF-1 receptors; 2) BSF-1 selectively induced class II antigen expression while anti-Lyb2 and anti-B220 induced the expression of other surface markers as well; and 3) PGE2 inhibited BSF-1 but not antibody-mediated class II induction. Finally, the presence of receptors for BSF-1 and the baseline expression of cell surface Ia was shown to be unlinked to Ig gene rearrangement and expression in this series of pre-B-cell lines. The independent regulation of Ia and Ig genes observed here may reflect a branching rather than a linear pathway for B-cell differentiation. The differentiation of pre-B-cells to mature Ig-secreting cells should probably not be defined solely by rearrangement of Ig genes, since this is likely to represent an oversimplified view of B-cell differentiation.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
authors.forename: B S
authors.initials: BS
authors.lastname: Polla
authors.forename: J
authors.initials: J
authors.lastname: Ohara
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
authors.forename: N
authors.initials: N
authors.lastname: Nabavi
authors.forename: A
authors.initials: A
authors.lastname: Myer
authors.forename: H C
authors.initials: HC
authors.lastname: Liou
authors.forename: F W
authors.initials: FW
authors.lastname: Shen
authors.forename: S
authors.initials: S
authors.lastname: Gillis
authors.forename: J V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: L H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D005802:Genes, MHC Class II; D006412:Hematopoietic Stem Cells / Q000276:immunology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D007518:Isoantibodies / Q000008:administration & dosage; D051379:Mice; D015398:Signal Transduction
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D007378:Interleukins; D007518:Isoantibodies; D015847:Interleukin-4