Stable and progressive CLL model. In stable CLL (ZAP-70^–), moderate levels of surface CCR7 expression facilitate low levels of CLL cell recruitment to the LN. Once within this environment they are stimulated to produce CCL17 and CCL21 that aid in the recruitment of CD4⁺CD40L⁺ Th cells that promote CLL proliferation and survival. In progressive CLL, ZAP-70⁺ CLL cells have a greater propensity to migrate to the LN, due to increased surface expression of CCR7. The higher numbers of CLL cells within this environment can recruit greater numbers of CD4⁺CD40L⁺ Th cells, leading to the formation of more proliferation centers. In addition, the ZAP-70⁺ CLL cells are more responsive to the survival factor CXCL12. Collectively this will result in an accumulation of CLL cells within the LN, a higher tumor burden, and cellular turnover.