The mouse B cell repertoire : antibody specificities and immunoglobulin (sub) class distribution

The total number of different immunoglobulin (I g) molecules that the immune system produces is often called the antibody specificity repertoire orB cell repertoire (Chapter 1). This repertoire can be subdivided into three categories: the potential, the available and the actual repertoires. The potential repertoire is determined by the number, structure and mechanisms of expression of the germl ine genes encoding lg molecules plus the possible somatic variants derived from them and can be regarded as what potentially can be made. The available repertoire is defined as the set of diverse antibody molecules that are expressed by immunocompetent but resting B lymphocytes and can be looked upon as what has been made and can be used. The actual repertoire is represented by that set of antibodies that is actually secreted by S cells and can be regarded as what is actually being used. Little is known about the regulatory mechanisms that enable the establishment, from the potential repertoire, of the available and functionally expressed repertoire of the immunocompetent resting B cell compartment. Similarly, the mechanisms that govern the establishment of the actual repertoire from the available repertoire are only partly known. Therefore~ the purpose of the studies presented in this thesis (as outlined in Chapter Ill) was to obtain more information concerning the regulatory mechanisms that are involved in the functional expression of the lg C and V genes by murine B cells. To this end, frequency analyses of B cells secreting particular lg heavy chain isotypes (C gene expression) and specific lgM antibodies (V gene expression) were performed among the progeny of B cells that had differentiated from pre-S cells in vitro. The same analyses were performed on in vivo generated mitogen-reactive S cells (available repertoire) and on the 1Spontaneously1 occurring ( 1background') lg-secreting cells (actual repertoire). The possible regulating influences studied include age, T cells and exogenous antigens. The latter became feasible, since, with the successful breeding of germfree mice fed an ultrafiltered solution of chemically defined low molecular weight nutrients, exogenous stimuli such as antigens and mitogens can be reduced to a minimum never attained before.