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 changes, including up-regulation of major histocompatibility complex class II molecules and expression of B7.2, which are required for initiating and sustaining a productive interaction with T helper cells. We have previously demonstrated that neonatal B cells fail to show a similar up-regulation of class II and B7.2 expression following B-cell receptor (BCR) ligation, although these responses could be induced by other stimuli. Here we demonstrate that immature B cells from adult bone marrow exhibit even more profound defects in these responses, as they fail to up-regulate class II in response to either BCR ligation or interleukin-4. Moreover, bone marrow-derived, immature B cells could not be induced to express B7.2 either by receptor cross-linking or by lipopolysaccharide. These differences in the inducible expression 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 induced in mature B cells by co-culture with bone marrow cells. Furthermore, short-term culture of bone marrow permitted B-cell maturation, which was accompanied by acquisition of responsiveness to the same stimuli as mature, splenic B cells. The inability of immature B cells to show these responses provides a molecular explanation for their reported deficiency in interacting with 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 compartment.
Marshall-Clarke
S
S
Department of Human Anatomy and Cell Biology, The University of Liverpool, New Medical School, Ashton Street, Liverpool, and Division of Immunology, Institute for Animal Health, Pirbright, Surrey, UK.
Tasker
L
L
Parkhouse
R M
RM
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D001853:Bone Marrow / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D011493:Protein Kinase C; D002118:Calcium