The isotype cycle: Successive changes in surface immunoglobulin classes expressed by the antigen-binding B-cell population during the primary in vivo immune response

Using the antigen-binding inhibition method, capable of revealing any combination of three surface Ig (sIg) isotypes on a population of antigen-binding cells (ABC) (S. Kanowith-Klein, E. S. Vitetta E.L. Korn, and R.F. Ashman, J. Immunol. 122, 2349, 1979) we have defined the sequence of antigen-induced changes in the expression of sIgM, sIgD, and sIgG on the sheep erythrocyte (SRC) antigen-binding B-cell population (SRC-ABC) throughout the in vivo primary immune response. The majority of nonimmune B-ABC simultaneously expressed M and D (M⁺D⁺G^-). By Day 3 sIgG had appeared, mainly on cells already bearing sIgM and sIgD. By Day 5, other G⁺ populations appeared: M⁺D^-G⁺ and M^-D^-G⁺. By Day 12, M⁺D^-G⁺ ABC declined, while M^-D^-G⁺ ABC remained predominant for another month. By 6 months, the sIg phenotypes on the ABC had returned to the original nonimmune pattern, mainly M⁺D⁺G^-; but the absolute number of 6-month immune ABC was four times greater than that of nonimmune ABC. This cyclical change in sIg expression was confined to the B-cell population expressing receptors specific for the immunizing antigen, and affected the large majority of such cells. Twelve days after immunization with SRC, ABC specific for a non-cross-reacting antigen still mainly expressed the nonimmune sIg phenotype, M⁺D⁺G^-.