Binding of malignant lymphoid cells to the white matter of the human central nervous system: role of different CD44 isoforms, beta 1, beta 2 and beta 7 integrins, and L-selectin.

Spreading of reactive and malignant lymphoid cells into the brain parenchyma requires regulated adhesion of the lymphoid cells to the parenchymal cells and/or extracellular matrix of the central nervous system. A multifunctional adhesion molecule CD44 partially mediates binding of lymphocytes to the white matter by interacting with hyaluronate. To analyze which forms of CD44 and what other adhesion molecules mediate this binding. Namalwa cells were transfected to express either standard (CD44st) or variant isoforms of CD44 containing exons v6-v10, v7-v10, and v8-v10. The binding of CD44st and CD44v6-v10 transfectants to human cerebellar white matter was tested and it was about 1.7- and 2-fold greater without and with PMA activation, respectively, compared with vector-transfected control cells. Hyaluronidase digestion of tissue sections decreased binding of CD44 expressing cells to the level of vector-transfected cells. Hermes-1, a monoclonal antibody recognizing the hyaluronate binding site of CD44, inhibited white matter adhesion of CD44v6-v10 and activated CD44st cells and binding of soluble hyaluronate to the CD44 transfectants. Transfectants also expressed beta 1, beta 2 and beta 7 integrins and L-selectin, but antibodies against these molecules did not inhibit adhesion to the white matter. These results suggest: (a) Addition of exons v6-v10 to the membrane proximal region of CD44 does not affect lymphoid cell adhesion to the white matter. (b) The only ligand of CD44 in the central nervous system (CNS) white matter is hyaluronate. (c) Additional adhesion mechanisms other than the ones analyzed above must exist.