Clones of B lymphocytes: their natural selection and expansion.

The operation of clonal selection for cells of the B-lymphocyte line is discussed with regard to: 1) The clonal repertoire determined by antigen binding to B lymphocytes, which is much larger than that determined by limiting dilution cloning assays. This quantitative difference is interpreted in terms of the multiple shared specificities of each antibody molecule. 2) Multiclonal responses and initial selection by antigen of particular clones (preferential primary selection). 3) Clonal dominance. During an immune response one clone (or a small number of clones) of B cells is preferentially selected and proliferated, apparently at random, from a heterogeneous population of cells capable of responding to the given antigen. Co-dominance of two or more clones simultaneously can be obtained by mixing selected clones. Secreted antibody is seen as playing a role in the establishment of clonal dominance. A model for clonal expansion is presented. The model attempts to explain the generation of memory and antibody secreting cells within each clonal expansion in terms of the ratio of two signals, one for proliferation and one for differentiation. The delivery of these signals is proposed to involve the receptor antibody-antigen interaction for proliferation and a self-recognition site interaction for differentiation.