Stromal cell-independent maturation of IL-7-responsive pro-B cells.
The proliferation, survival, and differentiation of B cell progenitors in primary hematopoietic tissues depends on extracellular signals produced by stromal cells within the microenvironment. IL-7 is a stromal-derived growth factor that plays a crucial role in B lineage development. We have shown that in the presence of IL-7, pro-B cells proliferate and differentiate to a stage in which they are responsive to stromal cells and LPS, leading to terminally differentiated IgM-secreting plasma cells. In this report, we examine in detail the role of stromal cells in the transition from the IL-7-responsive pro-B cell stage to the mature LPS-responsive B cell stage. We demonstrate that this transition fails to occur, even in the presence of stromal cells and LPS, if constant exposure to IL-7 is maintained. The transition from the large pro-B cell stage to the small cmu+ pre-B cell stage occurs independent of stromal cells. Moreover, the "stromal cell-dependent" maturation that occurs subsequent to the expression of surface IgM leading to responsiveness to B cell mitogens can also be accomplished in the absence of stromal cells if pre-B cells are cultured in proximity to each other or at high cell concentrations. Together these results suggest that stromal cells mediate B cell differentiation by providing the necessary growth requirements (i.e., IL-7) to sustain the development of pre-B cells. The progeny of these pre-B cells can then differentiate through as yet unidentified homotypic interactions, leading to the production of LPS-responsive B cells.
Ray
R J
RJ
The Ontario Cancer Institute and Department of Immunology, University of Toronto, Canada. ray@oci.utoronto.ca
Stoddart
A
A
Pennycook
J L
JL
Huner
H O
HO
Furlonger
C
C
Wu
G E
GE
Paige
C J
CJ
D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007075:Immunoglobulin M / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D017154:Stromal Cells / Q000166:cytology
D018941:Antigens, CD19; D007075:Immunoglobulin M; D015851:Interleukin-7; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell