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Stromal Cells Attract B‐Cell Progenitors to Promote B‐Cell–B‐Cell Contact and Maturation
Author(s) -
Milne C. D.,
Zhang Y.,
Paige C. J.
Publication year - 2005
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2005.01612.x
Subject(s) - stromal cell , cell , progenitor cell , microbiology and biotechnology , mesenchymal stem cell , biology , stem cell , cancer research , genetics
The in vitro differentiation of B‐lineage progenitors into Ig‐secreting mature B cells has classically required a co‐culture system containing lipopolysaccharide (LPS) and stromal cells. We have previously showed that B‐lineage progenitors cultured in round‐bottomed wells can mature and secrete immunoglobulin M (IgM) on par with cultures containing stromal cells. This clearly demonstrates that any factors essential for progenitor cell maturation can be found in cultures containing media, serum, LPS and B‐cell progenitors. However, stromal cells are important for the maturation observed when cells are cultured in flat‐bottomed wells. We hypothesized that stromal cells may attract B‐cell progenitors and promote contacts between responsive cells, a phenomenon that is mimicked by the cultures in round‐bottomed wells. In this study, we explore how stromal cells accomplish these functions. We show that stromal cells attract B‐cell progenitors in a pertussis toxin‐sensitive manner. The stromal cell line S17 produces the chemokine CXCL12, which is able to induce the chemotaxis of B‐lineage progenitors. Chemotaxis can be blocked by a small peptide inhibitor (T134) of CXCR4, the CXCL12 receptor. Further, disrupting chemotaxis can reduce the supportive role played by S17 when B‐lineage progenitors are cultured in flat‐bottomed wells.