Emergence and Evolution of Secondary Lymphoid Organs

Abstract

For effective adaptive immunity to foreign antigens (Ag), secondary lymphoid organs (SLO) provide the confined environment in which Ag-restricted lymphocytes, with very low precursor frequencies, interact with Ag on Ag-presenting cells (APC). The spleen is the primordial SLO, arising in conjunction with adaptive immunity in early jawed vertebrates. The spleen, especially the spleen's lymphoid compartment, the white pulp (WP), has undergone numerous modifications over evolutionary time. We describe the progressive advancement of splenic WP complexity, which evolved in parallel with the increasing functionality of adaptive immunity. The Ag-presenting function of follicular dendritic cells (FDC) also likely emerged at the inception of adaptive immunity, and we propose that a single type of hematopoietically derived APC displayed Ag to both T and B cells. A dedicated FDC, derived from a vascular precursor, is a recent evolutionary innovation that likely permitted the robust affinity maturation found in mammals.

Keywords: adaptive immunity; antigen presentation; evolution; spleen; white pulp.

Figure 1

Progressive accumulation of splenic white pulp complexity and functionality over the course of vertebrate evolution. The columns at left denote the presence of indicated cell types, substructures, or processes in the species shown in the middle of the figure. The timeline (middle) shows the estimated date of the last common ancestor shared between humans and the indicated species. At right, graphical representations of white pulp microarchitecture and cellular constituency (as well as germinal center composition, when present) are indicated in the species shown in the timeline. Abbreviations shown at left: CSR, class switch recombination; FDC, follicular dendritic cell; GC, germinal center; GS, Grenzschichtmembran of Sterba; LN, lymph node; MYA, million years ago; PP, Peyer’s patch; RP, red pulp; SHM/AM, somatic hypermutation/affinity maturation; WP, white pulp. Data from Mebius & Kraal (2005) for mammals; Yasuda et al. (1998, for birds; Leceta & Zapata (1985, for reptiles; Baldwin & Cohen (1981) for amphibians; Flajnik & Du Pasquier (2013) for bony fish; and Fange & Pulsford (1983), Rumfelt et al. (2002), and Castro et al. (2013) for cartilaginous fish.