1. Expression of CD28 by bone marrow stromal cells and its involvement in B lymphopoiesis.
- Author
-
Gray Parkin K, Stephan RP, Apilado RG, Lill-Elghanian DA, Lee KP, Saha B, and Witte PL
- Subjects
- Aging immunology, Animals, B-Lymphocyte Subsets metabolism, Bone Marrow Cells cytology, CD28 Antigens genetics, CD28 Antigens metabolism, CD28 Antigens physiology, Cell Communication immunology, Cell Division immunology, Cell Line, Cell Lineage immunology, Cell Survival immunology, Cells, Cultured, Female, Ligands, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Stem Cells cytology, Stem Cells immunology, Stromal Cells immunology, Stromal Cells metabolism, Stromal Cells physiology, T-Lymphocyte Subsets cytology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, B-Lymphocyte Subsets cytology, B-Lymphocyte Subsets immunology, Bone Marrow Cells immunology, Bone Marrow Cells metabolism, CD28 Antigens biosynthesis, Cell Differentiation immunology
- Abstract
Young mice lacking CD28 have normal numbers of peripheral B cells; however, abnormalities exist in the humoral immune response that may result from an intrinsic defect in the B cells. The goal of this study was to assess whether CD28 could be involved in the development of B cells. CD28 mRNA was detected preferentially in the fraction of bone marrow enriched for stromal cells. Flow cytometry and RT-PCR analysis demonstrated that CD28 was also expressed by primary-cultured stromal cells that supported B lymphopoiesis. Confocal microscopy revealed that in the presence of B-lineage cells, CD28 was localized at the contact interface between B cell precursors and stromal cells. In addition, CD80 was detected on 2-6% of freshly isolated pro- and pre-B cells, and IL-7 stimulation led to induction of CD86 on 15-20% of pro- and pre-B cells. We also observed that stromal cell-dependent production of B-lineage cells in vitro was greater on stromal cells that lacked CD28. Finally, the frequencies of B-lineage precursors in the marrow from young (4- to 8-wk-old) CD28(-/-) mice were similar to those in wild-type mice; however, older CD28(-/-) mice (15-19 mo old) exhibited a 30% decrease in pro-B cells and a 50% decrease in pre-B cells vs age-matched controls. Our results suggest that CD28 on bone marrow stromal cells participates in stromal-dependent regulation of B-lineage cells in the bone marrow. The localization of CD28 at the stromal cell:B cell precursor interface suggests that molecules important for T cell:B cell interactions in the periphery may also participate in stromal cell:B cell precursor interactions in the bone marrow.
- Published
- 2002
- Full Text
- View/download PDF