Precursor B Cell Receptor-Dependent B Cell Proliferation and Differentiation Does Not Require the Bone Marrow or Fetal Liver Environment

doi:10.1084/jem.191.1.23

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© The Rockefeller University Press, 0022-1007/2000/1/23/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 1, January 3, 2000 23-32

Original Article

Precursor B Cell Receptor–Dependent B Cell Proliferation and Differentiation Does Not Require the Bone Marrow or Fetal Liver Environment

Antonius G. Rolink^a, Thomas Winkler^b, Fritz Melchers^a, and Jan Andersson^a

^a Basel Institute for Immunology, CH-4005 Basel, Switzerland
^b Department of Immunology, Friedrich-Alexander University, D-91054 Erlangen, Germany
Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland.41-61-605-136441-61-605-1265

rolink{at}bii.ch

The capacity of precursor B (pre-B) I cells from fetal liverand bone marrow to proliferate and differentiate into surfaceimmunoglobulin–positive immature B cells in vitro wasanalyzed. Both fetal liver– and bone marrow–derivedprogenitors do so in a pre-B cell receptor (pre-BCR)–dependentmanner in tissue culture medium alone, without addition of othercells or cytokines. Approximately 20% of the initial pre-B Icells enter more than one division. Analyses at the single-celllevel show that $~$ 15% divide two to five times. Coculture of pre-BI cells with stromal cells did not enhance proliferation ordifferentiation, whereas the presence of interleukin 7, especiallyin combination with stromal cells, resulted mainly in the expansionof pre-B I cells and prevented their further differentiation.Thus, the environment of fetal liver or bone marrow is not requiredfor the pre-BCR to exert its function, which is to select andexpand cells that have undergone an inframe V_H-D_HJ_H rearrangementthat produces a pre-BCR–compatible µH chain. Itappears unlikely that a ligand for the pre-BCR drives this pre-Bcell proliferation.

Key Words: B cell development • precursor B cell receptor • ${lambda}$ ₅ • c-kit • bcl-2

Abbreviations used in this paper: BCR, B cell receptor; B6,C57BL/6; cµ, cytoplasmic µH chain; pre-B cell, precursorB cell; pro-B cell, progenitor B cell; sIg, surface Ig; SL chain,surrogate L chain.

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