Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis.
The bone marrow (BM) is well known to be the major site of Ig production in secondary immune responses; thus, the microenvironment of BM is considered to be essential for final differentiation of plasma cells. We identified in the peripheral blood (PB) early plasma cells (CD38++CD19+VLA-5-) committed to entering the BM. The sorted early plasma cells rapidly entered apoptosis in vitro, but these cells could survive and further differentiate into mature plasma cells (CD38 CD19+) just as BM plasma cells in the presence of a BM-derived stromal cell line (KM-102). Culture supernatants of KM-102 cell lines could also support survival of these cells, and antibody to interleukin-6 (IL-6) completely blocked the effect of these supernatants. Furthermore, recombinant IL-6, but not IL-1 or IL-3, could support their survival and their differentiation into mature plasma cells (CD38 CD19+VLA-5+) with expression of VLA-5 mRNA. Therefore, here is direct evidence that early plasma cells found in the PB differentiated into mature plasma cells with stromal cell-derived IL-6 in vitro; thus, BM stromal cells control the final checkpoint of plasma cell differentiation with secretion of IL-6 in the BM.
Kawano
M M
MM
Department of Hematology and Oncology, Hiroshima University, Japan.
Mihara
K
K
Huang
N
N
Tsujimoto
T
T
Kuramoto
A
A
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology; D001483:Base Sequence; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003095:Collagen Diseases / Q000097:blood / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000502:physiology*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1