Increased phosphatidylinositol metabolism is an important but not an obligatory early event in B lymphocyte activation.
The phosphatidylinositol (PI) response has been implicated in membrane signaling and cell activation. The role of phospholipid metabolism among the early events in B cell activation has not been clear. We have treated murine B cells with anti-Ig antibody and lipopolysaccharide (LPS) and have found that, although anti-IgM induces the PI response, LPS does not. The increase in metabolic labeling of PI is specific to PI, and not the phosphatidylinositols. Anti-IgM unresponsive B cells from CBA/N mice, which may correspond to a specific functional subpopulation of normal B cells, do not increase PI metabolism in response to anti-IgM, nor do they undergo blastogenesis or DNA synthesis. Moreover, when these deficient B cells are given a stimulus sufficient to drive them into S (LPS + anti-IgM), there is still no corresponding activation of PI metabolism. These results are consistent with a two-signal model of xid B cell activation by anti-IgM. One very early signal primes the cells but does not induce the PI response. A second early signal is supplied by LPS. This signal sustains cells in the activated state, allowing them to receive yet other signals to proceed through G1 and progress further along the cell cycle. A similar sequence of events may occur in the normal B cell, with the first signal provided by priming with anti-IgM, and the second signal, the PI response, supported by a sufficiently high dose of anti-IgM to induce PI turnover and maintain the cell in G1.
Grupp
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Harmony
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D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000502:physiology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010716:Phosphatidylinositols / Q000378:metabolism*; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D000511:alpha-Macroglobulins; C044203:anti-IgM; C032306:polyclonal B cell activator; D004247:DNA