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A number of investigators have demonstrated the association of CD5+ (Ly-1/Leu-1) B cells with autoimmunity, excessive B-cell proliferation, and transformation. Previous work from our laboratory, among others, suggests that the selective advantage of this frequently autoreactive B-cell subset is to provide activation signals to conventional antigen-specific B cells. If one current hypothesis is correct then the overrepresentation of CD5+ B cells in some diseases and their novel capacity to act as helper cells reflect the activities of a separate B-cell lineage. Because of these observations it is of particular interest to evaluate the factors which contribute to the maturation of the CD5+ B-cell subset. The possibility that CD5+ B cells produce a factor or factors capable of influencing their own development was the focus of the present investigation. Rather than attempt to obtain soluble factors from heterogeneous CD5+ B-cell populations which could be contaminated with cytokine secreting monocytes or which could require as yet undefined activation signals in order to secrete putative factors, we chose to evaluate the production of CD5+ B-cell inducing factor(s) by monoclonal CD5+ B-cell hybridomas. Added incentive to this approach was provided by the observation that these hybridomas elaborate a factor(s) which, together with (NPb) idiotype-specific antibody produced by the hybridoma, substitutes for CD5+ B-cell populations in activating antigen-specific (NPb idiotypic) B cells in vitro. Furthermore, because of the low percentage of CD5+ B cells in the spleen and their relatively low level of CD5 antigen expression, we employed a sensitive functional assay rather than surface antigen expression alone to detect small numbers of mature CD5+ B helper cells. With this previously described system it was possible to observe the induction of functional CD5+ B cells following a 40 h culture of apparently CD5- B-cell populations with a 19-22 kd factor or factors derived from a CD5+ B hybridoma. Data presented here and elsewhere suggest that this CD5+ B-cell inducing activity is not mediated by IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, GM-CSF, or TNF. The role that such a B cell derived, B-cell directed factor may play in immunity and disease is discussed. |
