The in vitro derivation of phenotypically mature and diverse B cells from immature spleen and bone marrow precursors.
The capacity of immature B cells of the spleen and bone marrow to differentiate in vitro into cells representing mature end stage cells was investigated using B-cell activating factor belonging to the TNF family (BAFF) and Notch pathway activators. Immature splenic and bone marrow B cells were found, in the presence of both of these activators, to mature into cells with follicular mature (FM) and marginal zone (MZ) cell phenotypes. Such cells were functionally responsive to B-cell-specific activation. The derivation in vitro of cells with an MZ phenotype was more robust from CD23(-) populations than CD23(+) immature/transitional B cells, suggesting a direct immature/T1 B cell to MZ cell differentiation pathway. Transcript analysis of the in vitro-derived B-cell populations demonstrated expression profiles similar to maturing B cells in vivo. FACS-purified populations of B220(+)CD19(+)CD21(-)CD23(-) cells from bone marrow of 2-wk-old mice gave rise to populations of CD21(+)CD23(-) cells with MZ cell phenotypes as well as CD21(+)CD23(+) cells with FM cell phenotypes in percentages similar to those found in vivo. These data suggest that the commitment to an MZ and FM B cell phenotype is set prior to immature B-cell release from the marrow.
Roundy
Kirstin M
KM
Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Jacobson
Amanda C
AC
Weis
Janis J
JJ
Weis
John H
JH
D000818:Animals; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D018929:Cell Culture Techniques; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D016130:Immunophenotyping; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D051880:Receptors, Notch / Q000502:physiology; D013154:Spleen / Q000166:cytology*
D053264:B-Cell Activating Factor; D051880:Receptors, Notch