TY - JOUR
T1 - B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin α-dependent fashion
AU - Fu, Yang Xin
AU - Huang, Guangming
AU - Wang, Yang
AU - Chaplin, David D.
PY - 1998/4/6
Y1 - 1998/4/6
N2 - Lymphotoxin (LT)α is expressed by activated T cells, especially CD4+ T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTα- deficient (LTα(-/-) mice. LTα(-/-) mice produce high levels of antigen- specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTα-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTα(-/-) mice. It is not necessary for T cells to express LTα to support these immune functions. Importantly, LTα-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTα-expressing B cells, then LTα-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.
AB - Lymphotoxin (LT)α is expressed by activated T cells, especially CD4+ T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTα- deficient (LTα(-/-) mice. LTα(-/-) mice produce high levels of antigen- specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTα-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTα(-/-) mice. It is not necessary for T cells to express LTα to support these immune functions. Importantly, LTα-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTα-expressing B cells, then LTα-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.
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U2 - 10.1084/jem.187.7.1009
DO - 10.1084/jem.187.7.1009
M3 - Article
C2 - 9529317
AN - SCOPUS:0032489920
SN - 0022-1007
VL - 187
SP - 1009
EP - 1018
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -