Genes expressed during the IFNγ-induced maturation of pre-B cells

Interferon-gamma (IFNgamma) exerts diverse responses in B cell development ranging from growth arrest and apoptosis to proliferation and differentiation. IFNgamma stimulates murine 70Z/3 pre-B cells to express surface immunoglobulin (Ig) and this system serves as a useful model for the pre-B to immature B cell transition in B cell development. To analyze this developmental transition, we used a PCR-based subtractive hybridization in combination with miniarray screening to identify differentially-expressed genes in IFNgamma-stimulated compared with unstimulated 70Z/3 pre-B cells. The majority (44%) of the differentially-expressed genes obtained were known IFNgamma-inducible. These included multiple isolates from each of three multi-gene families, including two guanylate-binding protein (47 and 67 kDa GBP) families of GTPases and the hematopoietic IFNgamma-inducible nuclear protein family (HIN-200). These mulitiple isolates of genes comprised the majority of the total isolated and sequenced clones. Other known IFNgamma-induced genes in this group included Igkappa light chain and Ly-6, as well as genes with functions in antigen processing, cellular regulation, and cytoskeletal organization. Another 36% of the genes identified were previously known, but not known to be IFNgamma-inducible (e.g. pre-B cell enhancing factor, PBEF). The remaining 20% of the IFNgamma-induced isolates did not match entries in Genbank, and thus, may represent novel genes involved in IFNgamma responses and/or in the pre-B to immature B cell transition. Overall, the majority of the individual genes isolated were either not known to be IFNgamma responsive or were not previously known. (C) 2002 Elsevier Science Ltd. All rights reserved.