T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors.

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Abstract
Cloned murine helper T cells, restricted to the Iab antigens of the major histocompatibility locus and specific for horse erythrocytes as a foreign antigen, produce, in cooperation with antigen and histocompatible adherent cells, soluble factors that replace the helper T cells in their action on B cells. The following 3 types of factors can be distinguished on the basis of MW proteins having apparent MW 30,000 (p30) that act antigen- and Ia-nonspecifically as replication- and maturation-inducing factors and proteins having apparent MW 55,000 (p55) and 125,000 (p125) that act on resting B cells in an Ia-specific, restricted fashion. Neither horse erythrocytes (a T cell specific antigen) nor p55 and p125, alone or together, stimulate resting B cells to proliferation and maturation. Double occupancy by antigen and p55 or p125 renders Ia-compatible, but not Ia-incompatible, resting B cells susceptible to stimulation. The subsequent addition of p30 to these excited B cells then results in the proliferation and maturation of clones of horse erythrocyte-specific B cells. p55, but not p125, also cooperates with a bystander antigen, sheep erythrocytes, to excite sheep erythrocyte-specific resting B cells, which then replicate under the stimulatory action of p30. p30 do not bind antigen, nor do they bind anti-Ia or anti-immunoglobulin antibodies, p55 are bound by anti-H chain variable region antibodies, but not by anti-H or anti-L chain constant region antibodies or anti-Ia antibodies. p125 molecules bind horse but not sheep erythrocytes and are bound by anti-H chain variable region, but not by anti-H or L chain constant region or anti-Ia antibodies. p55 and p125 are likely to be soluble analogues of the antigen-specific, Ia-restricted T cell receptors of the cloned helper T cells.