A. R. Williamson’s research while affiliated with MRC National Institute for Medical Research and other places

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.

The primary anti-NP response in C57BL/6 and CBA mice was analyzed by isoelectric focusing. Antibody responses in C57 mice were restricted in heterogeneity and over 80 % of this strain shared an isoelectric focusing spectrum characteristic of an homogeneous antibody (spectrotype). This spectrotype N-l was inherited as a dominant characteristic in (CBA×C57)F1 mice, and backcross analysis revealed that it was genetically linked to the heavy chain allotypeIg-1 b . It thus behaved as a marker similar to the fine specificity characteristic of heteroclitic antibody. Elution studies showed that antibody with the spectrotype N-1 was heteroclitic, with a higher affinity for NIP and NNP than for the immunogen NP. It is argued that a) a single germ-lineV gene (designated N-1) codes for the VH region of this antibody and b) in C57BL/6 mice this geneV H N-1 is closely linked toIg-1 b .

Clonal expansion of B cells has been explored during a primary response and during propogation of a single selected clone (S13). In both cases the development of B memory was studied in relation to the generation of antibody forming cells (AFC).

A single clone of B cells producing anti-DNP antibody recognizable by the isoelectric-focusing spectrum has been used, in a double transfer system, to study clonal memory. Trasnsferable B memory develops between 4 and 7 days after the first transfer with antigen. B-memory cells thus proliferate before or concomitantly with antibody-forming cells.

A single clone of B cells producing anti-DNP antibody recognizable by the isoelectric-focusing spectrum has been used, in a double transfer system, to study clonal memory. Trasnsferable B memory develops between 4 and 7 days after the first transfer with antigen. B-memory cells thus proliferate before or concomitantly with antibody-forming cells.