Cross-linking of Membrane Immunoglobulin D, in the Absence of T C Help, Kills Mature B cells in Vivo

The Journal of Experimental Medicine, 1995, 181: 515-525

By Fred D. Finkelman, Joanne M Holmes, Oksana I Dukhanina, and Suzanne C. Morris

The authors seek to determine whether B cells, in vivo, that have had their surface Ig cross-linked (first signal) in the absence of T cell help, return to a resting state, survive but become anergic, or die.

In these studies, Finkelman et al. intravenously injected various monoclonal antibodies to IgD that have varying abilities to cross-link the antibodies on the surface of B cells. Immature B cells express IgM initially, and as they mature, may also express IgD. The generation of new B cells and the generation of T cell help were blocked with the use of specific reagents. One day after treatment with a monoclonal antibody know to cross-link IgD, the number of B cells had not decreased, but after five to seven days, the number of early B cells in the spleen decreased two to five fold, indicating that they were dying. No increase in these specific B cells was seen in the lymph nodes, suggesting that cells were dying rather that migrating out the spleen. These results are consistent with the results of Goodnow for the double-transgenic model discussed above.

The authors further observed that 10 mg was not sufficient to kill effectively while 100 mg was. Furthermore, although 10 mg was sufficient to begin the signaling process, higher amounts, available for a longer period of time (24 hours) were required to cause B cell loss. In a final experiment, mice treated with anti-IgD and with a stimulator of T cell help did not lose a large number of specific B cells. The authors suggest that T cell help is required to block deletion, but is not always available in time to arrest the process of cell death.