Figure 8.

Proposed schematic of B cell selection during a normal versus impaired humoral immune response during LCMV infection. In (A), antigen specificity of the resultant Ab response is facilitated by effective selection of B lymphocytes in the LZ of the GC response. Some of these cells migrate to the periphery as effector cells while others cycle back into the DZ for proliferation in an iterative process. During LCMV and more generally, other chronic infections (B), the high concentration of IFN-I along with sustained elicitation and T_FH expansion triggers selection of non-specific B cells in the context of a disrupted follicular architecture; as such, antigen-specific effector cells and consequently, Ab responses, are “drowned” out by the influx of non-specific cells. This figure only represents a snapshot of the process in which the immune response is further honed in (A), whereas the dilution and loss of specificity in (B) is exacerbated in subsequent rounds.