IgM(+)IgD(+)CD27(+) B cells from peripheral blood have been described as circulating marginal zone B cells. It is still unknown when and where these cells develop. These IgM(+)IgD(+)CD27(+) B cells exhibit somatic hypermutations (SHMs) in their B cell receptors, but the exact nature of the signals leading to induction of these SHMs remains elusive. Here, we show that IgM(+)IgD(+)CD27(+) B cells...

Lymph node (LN) development depends on prenatal interactions occurring between LN inducer and LN organizer cells. We have distinguished defects in LN formation due to failure in embryonic development (aly/aly) from defects in postnatal maturation (Il2rgamma(-/-)Rag2(-/-)). Both mutant strains form normal primordial LNs with differing fate. In aly/aly mice, the LN primordium dissipates irreversi...

The colonization of land by tetrapod ancestors is one of the major questions in the evolution of vertebrates. Despite intense molecular phylogenetic research on this problem during the last 15 years, there is, until now, no statistically supported answer to the question of whether coelacanths or lungfish are the closest living relatives of tetrapods. We determined DNA sequences of the nuclear-e...

Embryonic stem (ES) cells are a novel source of cells, especially hematopoietic progenitor cells that can be used to treat degenerative diseases in humans. However, there is a need to determine how ES cell-derived progenitors are regulated by both the adaptive and innate immune systems post transplantation. In this study, we demonstrate that hematopoietic progenitor cells (HPCs) derived from mo...

Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contr...

Antineutrophil cytoplasmic autoantibodies (ANCAs) are identified in the circulation of approximately 80% of patients with pauci-immune necrotizing and crescentic glomerulonephritis and systemic small vessel vasculitis, such as microscopic polyangiitis and Wegener granulomatosis. The most common antigen target for ANCAs is myeloperoxidase (MPO), which is found in neutrophils and monocytes. We re...

The RAG proteins are comprised of core endonuclease domains and noncore regions that modulate endonuclease activity. Mutation or deletion of noncore RAG regions in humans causes immunodeficiency and altered TCR repertoire, and mice expressing core but not full-length Rag1 (Rag1(C/C)) or Rag2 (Rag2(C/C)) exhibit lymphopenia, reflecting impaired V(D)J recombination and lymphocyte development. Rag...