The strict regulation of lymphocyte migration to splenic white pulp does not involve common homing receptors

Although the spleen is the largest secondary lymphoid organ, little is known about the regulation of lymphocyte migration towards its different compartments of red and white pulp, in contrast to the well-studied mechanisms of lymphocyte homing to lymph nodes. Here we show that short-term trypsin treatment of lymphocytes cleaved off molecules involved in entry into lymph nodes, while homing to the splenic white pulp was unaltered. Prolonged trypsin treatment also abolished the ability of lymphocytes to enter the white pulp. Analysis of affected cell surface molecules and adoptive transfer studies in combination with blocking antibodies revealed that l-selectin, CD44, PSGL-1 and the alpha(4) integrins are not required for migration to the white pulp. Although lymphocyte function-associated antigen-1 (LFA-1) is critical for entry into lymph nodes, we show here that in the absence of functional LFA-1 molecules, lymphocytes can still enter the white pulp, in spite of the high expression of intercellular adhesion molecule-1 on sinus lining cells in the marginal zone. The data indicate that adhesion molecules involved in lymphocyte homing to lymph nodes are not essential for migration towards the splenic white pulp, but that additional, trypsin-sensitive, and so far unidentified, molecules are required.