Differentiation Of Antibody-secreting Cells Research Articles

Analysis of long-lived plasma cell production and regulation: Implications for vaccine design for aquaculture

The importance of long-lived plasma cells (LPC), over other antibody-secreting cells (ASC), in the generation of long-term immunity and memory in mammals has been the focus of considerable recent interest. Studies suggest that long-term immunity to infectious agents, such as viruses, may be primarily due to the expression of antibody from this unique population of ASC. Unfortunately due to the relative paucity of studies on teleost immune cells, virtually no information exists on LPC, or ASC diversity in these species. However, recent work in our laboratory has revealed that trout possess functionally diverse ASC populations, including plasmablasts, short-lived plasma cells and long-lived plasma cells. Importantly, as in mammals, these populations are not uniformly distributed among all immune tissues. This is of particular significance with respect to long-lived plasma cells, which appear to exclusively reside within, or migrate to, the anterior kidney. Previous teleost studies have operated under the assumption that all ASC are plasma cells. However, we have found that virtually the entire peripheral blood lymphocyte (PBL) ASC response is comprised of plasmablasts, while the trout plasma cell response resides within the anterior kidney. Thus, the assumption that the in vitro behavior of ASC from PBL is identical to that of plasma cells and that they are responsible for in vivo antibody responses, is flawed. Based on this information we propose an alternative model of functional differentiation and regional distribution of ASC in the trout and pose some important implications for the development of immunological memory and aquaculture vaccines based on this model.

Heterogeneity of B-cells.

Two rat monoclonal antibodies, NIM-R2 and NIM-R3, were prepared that only recognize B-cells in murine secondary lymphoid tissues. Both showed differential reactivity in that they reacted most strongly with nonoverlapping populations of B-cells. They also reacted differentially with some cells of the primary lymphoid tissue, recognizing 90-95% of bone marrow cells, again in a nonoverlapping manner and with NIM-R2 accounting for twice as many cells as NIM-R3. The antibody NIM-R2, but not NIM-R3, also recognized thymocytes and red blood cells. The determinant recognized by NIM-R2 is of interest because it fluctuates at four defined stages of B-cell development: pre-B to immature B, activation of mature B, differentiation of memory cells, and differentiation of antibody-secreting cells. Particularly noteworthy was the differential reactivity of NIM-R2 with virgin and memory B-cells. Those cells that stained strongly with the antibody gave excellent primary responses, but were unable to transfer secondary responses, whereas weakly stained B-cells transferred memory, but could not generate primary antibody responses in vitro. Thus NIM-R2 recognized a cell-surface determinant that presumably decreases in density as primary B-cells differentiate into memory B-cells. A survey of sIg, I-A, Fc receptors, and major glycoproteins of B-cells from spleen, Peyer's patches, mesenteric lymph nodes, and peripheral lymph nodes failed to reveal any major differences between the cells from these different lymphoid organs.