Tetraspanins are a family of membrane proteins that organize their molecular partners into signal transducing microdomains at the eukaryotic cell surface. There are two tetraspanins whose expression is restricted to immune cells, CD37 and CD53. Here we describe their critical though differing roles in humoral immunity.
CD37-/- mice have poor humoral responses and reduced numbers of IgG-secreting plasma cells in lymphoid organs. This is a result of increased apoptosis in germinal centers. CD37 is essential for the function of α4β1 integrin and for vascular cell adhesion molecule 1 (VCAM-1)-mediated survival of IgG-secreting cells. CD37 is required for the mobility and clustering of α4β1 integrin in the plasma membrane and the transduction of pro-survival α4β1 integrin-dependent Akt signaling in CD37-/- IgG-secreting cells.
By contrast CD53-/- mice have poor cellularity in peripheral lymph nodes, with a 50% reduction in the number of lymph node T cells and a striking 90% reduction in the number of lymph node B cells. Lymphocyte homing assays show a significant reduction in homing of T cells to peripheral lymph nodes and an almost complete ablation of B cell homing. The expression of the key lymph node homing receptor L-selectin (CD62L) is impaired in CD53-/- B cells, but curiously, not CD53-/- T cells
Taken together the data point to different but critical roles for tetraspanins in regulating adhesion molecule function in B cells, CD37 is critical for the function of α4β1 integrin, where CD53 is critical for L-selectin.