Several TNF superfamily members play key roles in early B cell maturation, homeostasis, differentiation, and activation. While BAFF R is required for normal B cell maturation, interactions between BAFF-BAFF R, BAFF-TACI, APRIL-BCMA, and CD40 Ligand-CD40 promote B cell differentiation and homeostasis. The interaction between CD40 Ligand and CD40 is necessary for germinal center B cell differentiation, and CD27 and CD30 are memory B cell markers. Interactions between CD27 Ligand, CD30 Ligand, or CD40 Ligand and their respective receptors are also involved in B cell co-stimulation by T cells or natural killer cells. TNF superfamily regulation of B cell homeostasis and activation may be contribute to immune deficiency disorders, autoimmune diseases, and cancer.