Architectural defects in the spleens of Nkx2-3-deficient mice are intrinsic and associated with defects in both B cell maturation and T cell-dependent immune responses
- Author(s)
- Tarlinton, D; Light, A; Metcalf, D; Harvey, RP; Robb, L;
- Details
- Publication Year 2003-04-15,Volume 170,Issue #8,Page 4002-4010
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Mice lacking the homeodomain transcription factor Nkx2-3 are either asplenic or develop a spleen of significantly reduced size with poorly organized white pulp. In this report, we analyze the effect of this mutation on B lymphocyte development and differentiation. Follicular dendritic cells in spleen, but not lymph node, of Nkx2-3(-/-) mice fail to express a developmental Ag (follicular dendritic cell-M2) and show an abnormal association with B cells, despite essentially normal expression of several chemokine genes. Bone marrow reconstitution studies show the splenic disorganization and absence of marginal zone B cells to be of stromal rather than hemopoietic origin. Furthermore, Nkx2-3(-/-) mice show an excess of conventional B cells in mesenteric lymph node and peritoneal cavity, whereas transitional B cells are rare in spleen but overrepresented in bone marrow. Finally, immunization of Nkx2-3(-/-) mice with a T cell-dependent Ag elicits clusters of germinal center B cells, although these fail to develop to the same extent as in controls and there is no evidence of affinity maturation in serum Ab. Similarly, Ab-forming cells fail to aggregate into foci early in the response. Collectively, these data indicate a substantial role for Nkx2-3 in, the correct association of lymphocytes and splenic stromal elements that is independent of chemokine expression.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- FOLLICULAR DENDRITIC CELLS; MARGINAL ZONE; AFFINITY MATURATION; GERMINAL-CENTERS; HOMING CHEMOKINES; EXPRESSION; RECEPTOR; COMPARTMENTS; SELECTION; RESPONSIVENESS
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Creation Date: 2003-04-15 12:00:00