Ja. Rehmann et Tw. Lebien, TRANSFORMING GROWTH-FACTOR-BETA REGULATES NORMAL HUMAN PRE-B-CELL DIFFERENTIATION, International immunology, 6(2), 1994, pp. 315-322
Light chain gene rearrangement during mammalian pre-B differentiation
generally occurs in an orderly manner, beginning with kappa genes and
proceeding through lambda genes. We have previously shown that human p
re-B cell differentiation in vitro leads to a skewing toward lambda ex
pression, resulting in a higher percentage of lambda+ cells than kappa
+ cells. We now report that the multifunctional polypeptide transformi
ng growth factor-beta (TGF-beta) exerts a selective inhibitory effect
on the acquisition of cell surface lambda light chains during in vitro
differentiation of normal human pre-B cells, giving rise to a balance
d ratio (approximately 1:1) of kappa+ to lambda+ cells that resembles
what normally exists in vivo. The TGF-beta effect was ablated using a
neutralizing anti-TGF-beta antiserum and TGF-beta had no significant e
ffect on the acquisition of kappa or surrogate light chains. Experimen
ts using highly enriched pre-B cells (90 - 95% cytoplasmic mu+) sugges
ted that the TGF-beta effect was directly on the pre-B cell or the pre
-B cell to mu+/lambda+ immature B cell transition. The following pepti
des, cytokines, and antibodies had no effect on light chain acquisitio
n or expression: substance P, vasoactive intestinal peptide, leu/met e
nkephalin, IL-1, IL-4, IL-7, anti-class II MHC, anti-CD24, anti-CD40,
and the CD10 inhibitor phosphoramidon. A selective regulatory role for
TGF-beta on normal human B cell development in the bone marrow microe
nvironment is suggested by these results.