Persistent Calcium Elevation Correlates with the Induction of Surface Immunoglobulin-Mediated B Cell DNA Synthesis
Abstract
Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ((Ca(2+)) sub i. These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low-level but persistent sustained or cyclic elevations in (Ca(2+)) sub i. In marked contrast, early and nonsustained elevations in (Ca(2+) ) sub i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran-antiIg conjugate which induced very high level of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in (Ca(2+)) sub i as detected by flow cytometry. Finally, B cells from X-linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in (Ca(2+)) sub i, but do not show persistent calcium elevations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1993
- Accession Number
- ADA268347
Entities
People
- Carl H. June
- Fred Finkelman
- Hidehiro Yamada
- Mark Brunswick
- Michael S. Ring
Organizations
- Naval Medical Research Center