Immature B lymphocytes from adult bone marrow exhibit a selective defect in induced hyperexpression of major histocompatibility complex class II and fail to show B7.2 induction
S. Marshall-clarke et al., Immature B lymphocytes from adult bone marrow exhibit a selective defect in induced hyperexpression of major histocompatibility complex class II and fail to show B7.2 induction, IMMUNOLOGY, 100(2), 2000, pp. 141-151
Mature B lymphocytes respond to antigen receptor ligation by phenotypic cha
nges, including upregulation of major histocompatibility complex class II m
olecules and expression of B7.2, which are required for initiating and sust
aining a productive interaction with T helper cells. We have previously dem
onstrated that neonatal B cells fail to show a similar up-regulation of cla
ss II and B7.2 expression following B-cell receptor (BCR) ligation, althoug
h these responses could be induced by other stimuli. Here we demonstrate th
at immature B cells from adult bone marrow exhibit even more profound defec
ts in these responses, as they fail to up-regulate class II in response to
either BCR ligation or interleukin-4. Moreover, bone marrow-derived, immatu
re B cells could not be induced to express B7.2 either by receptor cross-li
nking or by lipopolysaccharide. These differences in the inducible expressi
on of class II and B7.2 appear to be intrinsic to the B cells, as they were
retained in purified populations of B-lineage cells and could not be induc
ed in mature B cells by coculture with bone marrow cells. Furthermore, shor
t-term culture of bone marrow permitted B-cell maturation, which was accomp
anied by acquisition of responsiveness to the same stimuli as mature, splen
ic B cells. The inability of immature B cells to show these responses provi
des a molecular explanation for their reported deficiency in interacting wi
th T cells. Failure of immature B cells to inducibly express B7.2 may also
be important for the establishment of self tolerance in the B-cell compartm
ent.