['12', 'tremendous', 'attention', '(39).', 'Many', 'molecules', 'have', 'been', 'described', 'which', 'can', 'induce', 'B', 'cell', 'proliferation', '(46-', '49).', 'However,', 'little', 'is', 'known', 'about', 'the', 'signal', 'transduction', 'pathways', 'which', 'may', 'affect', 'proliferation.', 'The', 'current', 'studies', 'focus', 'on', 'two', 'highly', 'related', 'B', 'cell', 'growth', 'factors,', 'HMW-BCGF', 'and', 'Bb,', 'the', 'activation', 'fragment', 'of', 'Factor', 'B', 'of', 'the', 'alternative', 'pathway', 'of', 'complement.', 'HMW-BCGF', 'and', 'Bb', 'are', 'antigenically', 'related,', 'cause', 'proliferation', 'only', 'of', 'activated', 'B', 'cells,', 'and', 'compete', 'with', 'each', 'other', 'for', 'binding', 'to', 'the', 'cell', 'surface', '(14).', 'Since', 'the', 'two', 'growth', 'factors', 'are', 'highly', 'related,', 'we', 'expect', 'that', 'they', 'would', 'induce', 'proliferation', 'by', 'similar', 'mechanisms.', 'Nonetheless,', 'they', 'are', 'not', 'identical', 'molecules,', 'and', 'HMW-BCGF', 'has', 'effects', 'on', 'B', 'cell', 'physiology', 'which', 'are', 'not', 'shared', 'by', 'Bb.', 'For', 'example,', 'BCGF', 'can', 'increase', 'expression', 'of', 'its', 'own', 'receptor,', 'which', 'Bb', 'does', 'not', 'do.', 'Since', 'it', 'has', 'been', 'difficult', 'to', 'associate', 'particular', 'second', 'messengers', 'with', 'a', 'proliferative', 'signal', 'in', 'any', 'system,', 'we', 'reasoned', 'that', 'we', 'could', 'take', 'advantage', 'of', 'the', 'similarities', 'and', 'differences', 'between', 'Bb', 'and', 'HMW-BCGF', 'to', 'gain', 'insight', 'into', 'which', 'second', 'messengers', 'might', 'be', 'associated', 'with', 'the', 'proliferative', 'signal.', 'Intracellular', 'messengers', 'generated', 'by', 'the', 'two', 'in', 'common', 'would', 'be', 'more', 'likely', 'to', 'be', 'related', 'to', 'an', 'ultimate', 'proliferative', 'event', 'than', 'second', 'messengers', 'generated', 'from', 'one', 'or', 'the', 'other,', 'but', 'nat', 'both', 'growth', 'factors.', 'in', 'this', 'work,', 'we', 'have', 'examined', 'two', 'possible', 'secand', 'messengers', 'in', 'some', 'detail.', 'The', 'first', 'is', 'cAMP.', 'Cyclic', 'AMP', 'is', 'generated', 'during', 'stimulation', 'of', 'activated', 'B', 'cells', 'by', 'HMW-BCGF,', 'but', 'not', 'Bb.', 'Because', 'of', 'this', 'discrepancy,', 'we', 'tested', 'whether', 'cAMP', 'might', 'be', 'associated', 'with', 'a', 'discrepant', 'physiologic', 'effect,', 'the', 'expression', 'of', 'HMW-BCGF', 'receptors.', 'In', 'fact,', 'several', 'agents', 'which', 'increase', 'cAMP', 'ail', 'lead', 'to', 'increased', 'receptor', 'expression,', 'and', 'their', 'ability', 'to', 'affect', 'this', 'change', 'is', 'inhibited', 'by', 'the', 'PKA', 'inhibitor', 'HA', '1004.', 'Thus,', 'the', 'data', 'are', 'consistent', 'with', 'the', 'hypothesis', 'that', 'HMW-BCGF', 'enhances', 'receptor', 'expression', 'because', 'of', 'generation', 'of', 'cAMP;', 'the', 'failure', 'of', 'Bb', 'to', 'influence', 'HMW-BCGF', 'receptor', 'expression', 'Is', 'presumably', 'related', 'to', 'its', 'inability', 'to', 'induce', 'cAMP', 'accumulation.', 'The', 'kinetics', 'of', 'cAMP', 'accumulation', 'after', 'HMW-BCGF', 'stimulation', 'make', 'it', 'unlikely', 'that', 'the', 'receptor', 'is', 'directly', 'coupled', 'to', 'adenylate', 'cyclase', 'via', 'Gg', '(50).', 'indeed,', 'indomethacin', 'inhibited', 'cAMP', 'accumulation', 'in', 'B', 'cells', 'after', 'stimulation', 'with', 'HMW-BCGF', '(but', 'not', 'cholera', 'toxin},', 'demonstrating', 'that', 'an', 'arachidonic', 'acid', 'metabolite', 'is', 'likely', 'involved', 'in', 'activation', 'of', 'adenylate', '“', 'cyclase', 'in', 'this', 'system', '(26,51).', 'Direct', 'measurement', 'of', 'PGE', 'accumulation', 'confirmed', 'the', 'generation', 'of', 'PGE', 'after', 'stimulation', 'with', 'HMW-BCGF', 'but', 'not', 'Bb.', 'This', 'observation', 'makes', 'it', 'likely', 'that', 'the', 'difference', 'between']