Polyclonal stimulation of normal splenic B lymphocytes with either lipopolysaccharide (LPS) or helper T lymphocytes specific for B cell surface antigens results in the selective expression of IgG subclasses by the secretory cells: in addition to IgM-secreting plaque-forming cells (PFC), thymus-independent stimulation leads to the development of IgG2 and IgG3 PFC, while helper cell-dependent activation leads to IgG1 and IgG2 PFC. This cannot be solely explained by selective stimulation of distinct B cell subpopulations, because purified LPS-reactive blasts if restimulated by helper cells switch to IgG1 while if maintained with LPS switch to IgG3. The simultaneous stimulation of splenic B cells with LPS and helper cells results in additive IgM and IgG2 responses, but in the selective suppression of IgG3 PFC with a concomitant synergic enhancement of IgG1 responses. These results are interpreted to indicate that the expression of IgG C genes in proliferating B lymphocytes is directed by the quality of nonspecific stimuli.
A new system to obtain large numbers of functionally competent hapten-specific effector helper T cells has been developed. Mice were primed in the tail with syngeneic spleen cells derivatized with one of three different haptens: 2,4,6-trinitrophenyl, fluorescein isothiocyanate and 3-(p-sulfophenyldiazo)-4-hydroxyphenyl. Draining lymph node cells were subsequently restimulated in culture with the homologous antigen for periods up to 6 weeks. More than 99% and 90% of the cells recovered from these preparative cultures, expressed Thy-1 and Lyt-1 antigens, respectively. These cells proliferated specifically in response to the homologous stimulation by haptenated syngeneic spleen cells, and they were found to display very high levels of hapten-specific helper activity, as assayed in a new, universal method for testing T -B cell cooperation, where every B cell can potentially respond to specific T cell help. Coculture of hapten-derivatized, functionally competent B cells with hapten-specific T cells obtained from the preparative cultures, resulted in the appearance, and exponential increase with time, of very large numbers of IgM and IgG plaque-forming cells. This helper activity could be shown to be: specific for the immunizing hapten and to increase with the time of in vitro helper cell enrichment, which also resulted in higher average avidities expressed by the helper cell populations. This methodology appears valuable for structural studies on hapten-specific helper cells, as well as for the functional analysis of effector helper -B cell interactions.
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