Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting

Alexei V. Tumanov, Sergei I. Grivennikov, Alexander N. Shakhov, Stanislav A. Rybtsov, Ekaterina P. Koroleva, Junji Takeda, Sergei A. Nedospasov, Dmitry V. Kuprash

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Abstract

Mice with reactivation of lymphotoxin β receptor (LTβR) system have profound defects in the development and maintenance of peripheral lymphoid organs. As surface LT is expressed by lymphocytes, natural killer cells, and lymphoid tissue-initiating cells as well as by some other cell types, we dissected cell type-specific LT contribution into the complex LT-deficient phenotype by conditional gene targeting. B-LTβ knockout (KO) mice displayed an intermediate phenotype in spleen as compared with mice with complete LTβ deficiency. In contrast, T-LTβ KO mice displayed normal structure of the spleen. However, inactivation of LTβ in both T and B cells resulted in additional defects in the structure of the marginal zone and in the development of follicular dendritic cells in spleen. Structure of lymph nodes (LN) and Peyer's patches (PP) was normal in both B-LTβ KO and T- and B-LTβ KO mice, except that PPs were of reduced size. When compared across the panel of lymphocyte-specific LT KOs, the defects in antibody responses to T-cell-dependent antigens correlated with the severity of defects in spleen structure. Expression of CCL21 and CCL19 chemokines was not affected in spleen, LN and PP of B-LTβ KO and T- and B-LTβ KO mice, while CXCL13 was slightly reduced only in spleen. Collectively, our data suggest the following: (i) requirements for LT signaling to support architecture of spleen, LN and PP are different; (ii) LT complex expressed by B cells plays a major role in the maintenance of spleen structure, while surface LT expressed by T cells provides a complementary but distinct signal; and (iii) in a non-transgenic model, expression of lymphoid tissue chemokines is only minimally dependent on the expression of surface LT complex on B and T lymphocytes.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalImmunological Reviews
Volume195
DOIs
Publication statusPublished - Oct 1 2003

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tumanov, A. V., Grivennikov, S. I., Shakhov, A. N., Rybtsov, S. A., Koroleva, E. P., Takeda, J., ... Kuprash, D. V. (2003). Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting. Immunological Reviews, 195, 106-116. https://doi.org/10.1034/j.1600-065X.2003.00071.x