Regulatory circuits and antibody responses

AbstractConsideration of the interactions among cells and cell products involved in regulating antibody responses leads us to suggest that such interactions are organized into several discrete circular series (circuits) integrated with one another by virtue of shared circuit components. We see these circuits as individually concerned with particular aspects of regulation (carrier‐specific, idiotype‐specific, etc.), but together constituting an integrated, self‐governing system capable of regulating all aspects of antibody production and assuring the ordedy progress of the response (sequential idiotype representation, affinity maturation, isotype representation, overall or selective non‐ responsiveness, etc.).To illustrate how a circuit‐based regulatory system could be constructed and expected to operate, we describe four integrated circuits here: a core regulatory circuit that determines whether a given idiotype will or will not be produced and three auxiliary regulatory circuits that respond to antigen and serum antibody (idiotype) levels by switching the core regulatory circuit into a suppression or “help” mode. These circuits incorporate the idiotype‐anti‐idiotype recognition system basic to the Jerne network theory but also provide for the operation of other cognitive systems that enable specific interactions between individual circuit elements (B cells, antibody, the various suppressor and helper T cells, macrophages and soluble regulatory products). As an integrated unit, the circuits constitute a detailed “working” model that depends on relatively few assumptions and is consistent with the known interactions between elements and the known properties of responses.