Expression of CD28 by bone marrow stromal cells and its involvement in B lymphopoiesis.
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.
Program for Immunology and Aging, Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA.
Kirstin
K
Gray Parkin
Robert P
RP
Stephan
Ron-Gran
RG
Apilado
Deborah A
DA
Lill-Elghanian
Kelvin P
KP
Lee
Bhaskar
B
Saha
Pamela L
PL
Witte
D000375:Aging / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018106:CD28 Antigens; D008024:Ligands