B cell dysfunction after bone marrow transplantation is associated with decreased Ca2+ flux upon membrane Ig crosslinking.
Patients undergoing bone marrow transplantation have a long-lasting defect of B cell-mediated immunity. Both quantitative (decreased blood B cell counts) and qualitative (decreased Ig production) abnormalities of B cells have been described. To better understand the mechanism of the qualitative defect and its potential relation to B cell immaturity, we studied the in vitro responsiveness of B cells to polyclonal stimuli in patients at 2-12 months post-transplant and in normal neonates. Several key steps of the B cell program were deficient in the patients while they were relatively normal in the neonates. These included (i) early activation as assessed by Ca2+ flux; (ii) late activation as assessed by the increase in cell size and upregulation of the activation antigens CD25 and CD71; and (iii) proliferation as assessed by the number of cycling cells after stimulation. We conclude that the functional B cell defect during the early (< 1 year) post-transplant period extends back to the level of early activation and cannot be simply attributed to the relative immaturity of post-transplant B cells.
Storek
J
J
Hart and Louise Lyon Immunology Laboratory, Division of Clinical Immunology/Allergy, Los Angeles, California 90024-1680.
Hultin
L E
LE
Ferrara
S
S
Ku
N
N
Giorgi
J V
JV
Champlin
R E
RE
Saxon
A
A
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D007111:Immunity, Cellular / Q000502:physiology; D007136:Immunoglobulins / Q000378:metabolism*; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000502:physiology; D008875:Middle Aged; D013997:Time Factors
D007136:Immunoglobulins; D002118:Calcium