The Carrier Effect and T Cell/B Cell Cooperation in the Antibody Response

his month's Pillars of Immunology papers by Av Mitchison (1, 2) from 1971 provided extensive evidence for an emerging consensus on the role of cellular cooperation in the Ab response.The papers are concerned with a phenomenon called the carrier effect, defined below, that was intensely studied at that time for clues to the nature of Ag recognition and the mechanisms of immunological memory and tolerance.Specifically, these papers mapped the carrier effect onto the new finding of cellular cooperation between T lymphocytes and B lymphocytes in the Ab response.In a paper in 1957 followed by a monograph in 1959, Macfarlane Burnet (3) proposed the clonal selection theory of Ab formation and launched the modern age of cellular immunology.In the 1950s and early 1960s, Peter Medawar, James Gowans, Jacques Miller, Robert Good, Baruj Benacerraf, and their colleagues, along with others, showed that lymphocytes are the agents of specific, adaptive immunity, and split immunity into two effector arms, cellular and humoral (Abmediated).Transfer experiments from immunized to naive animals demonstrated that cell-mediated immunity was responsible for graft rejection and delayed type hypersensitivity.Later in the 1960s, Jacques Miller (4, 5) and Henry Claman (6) and their colleagues showed that Ag-primed thymusderived lymphocytes (now called T cells) cooperated with bone marrow-derived lymphocytes (now called B cells) to enable Ab formation against sheep erythrocytes.B cells were shown to be the source of the specific Abs, but the role of Ag-specific T cells in the Ab response remained mysterious.This history is nicely reviewed by Mitchison (7).In 1967, I was a second year graduate student at the University of California, Berkeley, and my mentor, Leon Wofsy, kindly brought me along to the 1967 Cold Spring Harbor Symposium on Quantitative Biology.It was a very exciting time in immunology, and many of the leaders in Ab structure and genetics as well as the new field of cellular immunology were there.Many of the tools and concepts we take for granted had not yet been conceived: we did not have mAbs, flow cytometers, transgenic or knockout animals, or nucleic acid clones or sequences.The basic structure of Ab molecules had just been