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Changes in frequencies of clonable pre B cells during life in different
lymphoid organs of mice
A Rolink, D Haasner, S Nishikawa and F Melchers
Basel Institute for Immunology, Switzerland.
Progenitor and precursor B lymphocytes with the capacity of long-term
proliferation on stromal cells in the presence of interleukin-7 (IL-7) can
be cloned ex vivo from fetal liver, neonatal blood, and spleen, and from
adult bone marrow (BM) in frequencies that are similar in different strains
of mice and that change with age. A wave of clonable cells appears before
birth and disappears after birth in liver. Up to 2 weeks after birth, high
frequencies of clonable cells are present in spleen but become undetectable
at 6 to 8 weeks of age. In BM, high frequencies (1 in 50) of clonable cells
are present early after birth, and then decrease continuously to 10- to
20-fold lower levels at 6 to 8 months of age. The earliest clonable cells
have at least part of their IgH genes in germline configuration. Clones of
pro/pre B cells apparently continue to rearrange DH to JH segments on both
chromosomes. Rearrangements without insertion of N-sequences at the DHJH
joints are found in fetal liver, while DHJH joints in pre B cells of spleen
and BM throughout life have N-regions inserted. At least half of all
primary pre B-cell clones develop mitogen-reactive B cells after
differentiation to sIg+ B cells. Clonable pro and pre B cells are enriched
in B220- c-kit(low) as well as in B220+ c-kit+ and B220+ CD43+ cell
populations of BM. The frequencies of clonable cells in the B220-
c-kit(low) BM cell population decrease 10- to 20-fold during 8 months of
life, while those in the B220+ c-kit+ population remain constant, although
their absolute numbers drop 5- to 10-fold during that time. All long-term
proliferating clones express the surrogate L chain VpreB/lambda 5 as well
as c-kit and CD43 on all cells. The number of total clonable pro and pre B
cells is at best 10% of the number of cells required to produce the
estimated daily output of 5 x 10(7) B- lineage cells in a mouse. This
suggests that the production of a relatively constant number of B cells
during adulthood may be effected by precursors, which are not clonable on
stromal cells and IL-7 with long-term proliferative capacity. On the other
hand, BM transplantation experiments indicate that a mouse retains B220-
progenitors throughout life, from which pre B and B cells can be generated
in old mice in frequencies characteristic of young mice.
Volume 81,
Issue 9,
pp. 2290-2300,
05/01/1993
Copyright © 1993 by The American Society of Hematology
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