Pauciclonal B Cell Involvement in Production of Immunoglobulin in Scid Ig⁺ Mice

Abstract

Although the scid defect is complete in the majority of young and adult mice, ^~41% of those that are kept for nine months or more, develop some form of T and B cell involvement. The nature of the T cells that develop in these scid mice is described by Carroll et al. this volume. B cell involvement is characterized by the presence of large amounts of serum immunoglobulin in mice which were previously immunoglobulin negative. Mice which have high serum antibody titres have been called “leaky” and will be referred to as scid Ig⁺ in this text. Scid Ig⁺ mice have expressed µ, γ₁, γ_2b, γ₃ and κ; so far no γ_2b, α or λ production has been detected. We have isolated hybridomas from completely deficient and scid Ig⁺ mice. In independent fusions from scid mice no Ig producing hybridomas were obtained; however, large numbers of Ig producing hybridomas have been isolated from fusion of spleen cells of scid Ig⁺ mice. Analysis of the hybridomas isolated from scid Ig⁺ mice has revealed a restricted heterogeneity with respect to the κ light chains and the V_H regions expressed in the collection of hybridomas obtained from each individual mouse. Furthermore, idiotypes appear to be shared by immunoglobulins derived from some individual scid Ig⁺ mice analyzed. Preliminary studies suggested that in scid Ig⁺ mice the defect involved in the failure to produce normal B cells is overcome on rare occasions. The pauciclonal B cells that emerge proliferate in the absence of normal auto-regulatory mechanisms perhaps being activated by auto- or environmental antigens. That both stimuli may be involved is suggested by our finding that a proportion of antibodies from these scid ^Ig+ mice have specificity for nuclear antigens and antigens expressed by certain strains of Enterobacter and Serratia. As suggested by previous studies there appears to be a relationship between the T and B cells that appear in scid Ig⁺ mice. We show here that certain T cell populations can be expanded by administration of particular immunoglobulins isolated from hybridomas derived from scid Ig⁺ mice.