B Cell Heterogeneity in the Teleost Kidney: Evidence for a Maturation Gradient from Anterior to Posterior Kidney

Abstract

The fish immune system is quite different from the mammalian system because the anterior kidney forms the main site for hematopoiesis in this species. Using transcription factor-specific Abs derived from the murine system, together with anti-trout Ig Abs and Percoll gradient separation, we analyzed B cells from trout kidney sections and compared them to those from spleen and blood. For this study, immune cells were separated by Percoll gradients, and the resulting subpopulations were defined based on expression of B cell-specific transcription factors Pax-5 and B lymphocyte-induced maturation protein-1, as well as proliferative and Ig-secreting properties. Comparison of kidney, blood, and spleen B cell subsets suggest that 1) the anterior kidney contains mostly proliferating B cell precursors and plasma cells; 2) posterior kidney houses significant populations of (partially) activated B cells and plasmablasts; and 3) trout blood contains resting, non-Ig-secreting cells and lacks plasma cells. After LPS induction of resting B cells in vitro, the kidney and spleen have a high capacity for the generation of plasma cells, whereas the blood has virtually none. Our results indicate that trout B cell subsets are profoundly different among blood, anterior kidney, posterior kidney, and spleen. We hypothesize that developing B cells mature in the anterior side of the kidney and then migrate to sites of activation, either the spleen or the posterior kidney. Lastly, our data support the notion that the trout kidney is a complex, multifunctional immune organ with the potential to support both hemopoiesis as well as humoral immune activation.

Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

“…For example, the observation of high numbers of resting B cell profiles; small size (FSC + ), no secretory Ig (sIg − ), high mIg (mIg ++ ), nonproliferating (EdU − ), high Pax5 (Pax 5 ++ ), low Xbp1-S (Xbp1-S − ) within the blood and spleen (Fig. 6, Stage II) with contrastingly low numbers of the same within the anterior kidney [34,45,[50][51][52] parallels the high inducibility seen in the blood and spleen and lower inducibility in the anterior kidney (Fig. 5).…”

“…First, the kinetics, magnitude, and affinity of the TI and TD responses were quite similar. Both responses exhibited a relatively short primary phase versus a prolonged secondary and both maintained the high affinity achieved late in the primary (by week 16), even as the titers began to wane (week [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. This heightened affinity continued into the secondary, with even a slight increase (∼from −log aK 5.9 to 6.2), late in the secondary.…”

“…Parallel examination of mammalian and teleost memory may reveal evolutionarily universal mechanisms of memory generation. Tantalizing possibilities of such parallel features have been observed with long-lived plasma cell (LLPC) distributions in mammals [29][30][31] and teleosts [32][33][34], which home to their respective hematopoietic tissues, even though the organs themselves are different (i.e. bone marrow versus anterior kidney).…”

“…For example, perhaps the requisites for exceptionally high-titered, extensively mutated, high-affinity responses in * These authors contributed equally to this work. [32][33][34], which home to their respective hematopoietic tissues, even though the organs themselves are different (i.e. bone marrow versus anterior kidney).…”

“…partial diminution of the ASCs with HU). Thus, at times, resting MBCs or naive B cells must be present or transiting this tissue.Based on these functional analyses and previously reported correlative cytometric profiles [34,45,[50][51][52], our model of antigendependent trout B cell differentiation (Fig. 6) provides a number of useful correlative associations.…”