REGULATION OF EXPRESSION OF THE LIGAND FOR CD40 ON T-HELPER LYMPHOCYTES

Activated Th cells deliver contact-dependent signals to resting B lymp hocytes that initiate and drive B cell proliferation. Recently, a liga nd for the B lymphocyte membrane protein, CD40, has been identified th at delivers contact-dependent Th cell signals to B cells. A dimeric so luble form of CD40 was produced and used to further characterize the r egulation of expression of the CD40 ligand. Expression of the CD40 lig and was rapidly induced after Th lymphocyte activation, and its stabil ity depended upon whether Th cells were activated with soluble or plas tic-bound stimuli. Th cells activated with soluble stimuli rapidly tur ned over cell-surface CD40 ligand whereas Th cells activated with plas tic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuo us stimulation could maintain CD40 ligand expression. Ligation by solu ble CD40 could also stabilize expression of CD40 ligand on,the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthes is. In Con A-activated Th cells newly synthesized CD40 ligand exhibite d an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activ ation became more stable (10-h t1/2). In Th cells activated with plast ic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover e xcept that the rapid turnover phase began significantly later. This de lay could allow more time for newly synthesized CD40 ligand to assembl e or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cell s appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accesso ry proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cell s and may contribute to the high degree of specificity in B cell respo nses.