The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity.
Protective circulating Abs originate primarily from long-lived plasma cells in the bone marrow. However, the molecular and cellular basis of plasma cell longevity is unknown. We investigated the capacity of primary bone marrow-derived stromal cells to maintain plasma cell viability in vitro. Plasma cells purified from the bone marrow or lymph nodes died rapidly when plated in media, but a subpopulation of plasma cells survived and secreted high levels of Ab for up to 4 wk when cocultured with stromal cells. Ab secretion was inhibited by the addition of anti-very late Ag-4 to plasma cell/stromal cell cocultures indicating that direct interactions occur and are necessary between stromal cells and plasma cells. The addition of rIL-6 to plasma cells cultured in media alone partially relieved the sharp decline in Ab secretion observed in the absence of stromal cells. Moreover, when stromal cells from IL-6(-/-) mice were used in plasma cell/stromal cell cocultures, Ab levels decreased 80% after 7 days as compared with wild-type stromal cells. Further, IL-6 mRNA message was induced in stromal cells by coculture with plasma cells. These data indicate that bone marrow plasma cells are not intrinsically long-lived, but rather that plasma cells contact and modify bone marrow stromal cells to provide survival factors.
Minges Wols
Heather A
HA
Program for Immunology and Aging, Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
Underhill
Gregory H
GH
Kansas
Geoffrey S
GS
Witte
Pamela L
PL
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D039041:Integrin alpha4beta1 / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D039041:Integrin alpha4beta1; D015850:Interleukin-6; D012333:RNA, Messenger