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

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.