Precursor B cell receptor-dependent B cell proliferation and differentiation does not require the bone marrow or fetal liver environment.
The capacity of precursor B (pre-B) I cells from fetal liver and bone marrow to proliferate and differentiate into surface immunoglobulin-positive immature B cells in vitro was analyzed. Both fetal liver- and bone marrow-derived progenitors do so in a pre-B cell receptor (pre-BCR)-dependent manner in tissue culture medium alone, without addition of other cells or cytokines. Approximately 20% of the initial pre-B I cells enter more than one division. Analyses at the single-cell level show that approximately 15% divide two to five times. Coculture of pre-B I cells with stromal cells did not enhance proliferation or differentiation, whereas the presence of interleukin 7, especially in combination with stromal cells, resulted mainly in the expansion of pre-B I cells and prevented their further differentiation. Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe V(H)-D(H)J(H) rearrangement that produces a pre-BCR-compatible muH chain. It appears unlikely that a ligand for the pre-BCR drives this pre-B cell proliferation.
Rolink
A G
AG
Basel Institute for Immunology, CH-4005 Basel, Switzerland. rolink@bii.ch
Winkler
T
T
Melchers
F
F
Andersson
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005333:Fetus / Q000502:physiology; D015321:Gene Rearrangement; D007075:Immunoglobulin M / Q000032:analysis; D015851:Interleukin-7 / Q000502:physiology; D008099:Liver / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
D007075:Immunoglobulin M; D015851:Interleukin-7; D011498:Protein Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell