B-LYMPHOCYTES INDUCE THE FORMATION OF FOLLICULAR DENDRITIC CELL CLUSTERS IN A LYMPHOTOXIN ALPHA-DEPENDENT FASHION

Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD 4(+) T helper type 1 cells, and by activated B and natural killer cell s, but the functions of this molecule in vivo are incompletely defined . We have previously shown that follicular dendritic cell (FDC) cluste rs and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LT alpha-deficient (LT alpha(-/-)) mice. LT alpha(-/-) mice produce high levels of antigen-specific immunoglobulin (Ig)M, but ver y low levels of IgG after immunization with sheep red blood cells. We show here that LT alpha-expressing B cells are essential for the recov ery of primary, secondary, and memory humoral immune responses in LT a lpha(-/-) mice. It is not necessary for T cells to express LT alpha to support these immune functions. Importantly, LT alpha-expressing B ce lls alone are essential and sufficient for the formation of FDC cluste rs. Once these clusters are formed by LT alpha-expressing B cells, the n LT alpha-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells thems elves provide an essential signal that induces and maintains the lymph oid microenvironment essential for GC formation and class-switched Ig responses.