488-444 million years ago



The early vertebrates evolved lympocyte-like cells and many of the molecular components of the immune reactions of higher vertebrates.

In early vertebrates, there was a greater development of the branchial "thymus" (Shintani, 1999; Weichert, 1970). Lymphocytes evolved (or cells essentially indistinguishable from them) (Mayer, 2002). Lymphocyte-like cells in lampreys are small with little cytoplasm and produce lymphocyte transcription factors (Spi and Ikaros), CD45, BCAP, and CAST (which in mammals are primarily expressed in lymphocytes), CD98 and CD9 (which mammals use in lymphocyte proliferation and migration), proteasome subunits (PSMB4, PSMB7, 26S subunit pUb-R3, PSMA2, PSMA6, and PSMF1), and ABC9 (similar to the ABC proteins which mammals use to transport peptides to the MHC)., the complement protein C1q, and a number of other genes expressed in mammalian lymphocytes (hepsin, sygin 2, RAMP4, and talin) (Mayer, 2002; Shintani, 1999). Much of the expansion of the expansion of the interleukin family has occurred recently in separate events in early vertebrates and mammals (Huising, 2004). Lampreys possess homologs of C3, MASP, factor B (which has 3 SCR domains like those of gnathostomes and unlike sea urchins which have 5), and probably possess complement receptors. Both hagfish and lamprey C3 function in opsonization (Zarkadis, 2001).