The Internal Conduit System of the Swine Inverted Lymph Node

Abstract

Lymph nodes (LN) are the crossroad where naïve lymphocytes, peripheral antigens and antigen presenting cells contact together in order to mount an adaptive immune response. For this purpose, LN are highly organized convergent hubs of blood and lymphatic vessels that, in the case of B lymphocytes, lead to the B cell follicles. Herein take place the selection and maturation of B cell clones producing high affinity antibodies directed against various antigens. Whereas the knowledge on the murine and human LN distribution systems have reached an exquisite precision those last years, the organization of the antigens and cells circulation into the inverted porcine LN remains poorly described. Using up to date microscopy tools, we described the complex interconnections between afferent lymphatics and blood vessels, perifollicular macrophages, follicular B cells and efferent blood vessels. We observed that afferent lymphatic sinuses presented an asymmetric Lyve-1 expression similar to the one observed in murine LN, whereas specialized perifollicular sinuses connect the main afferent lymphatic sinus to the B cell follicles. Finally, whereas it was long though that mature B cells egress from the inverted LN in the T cell zone through HEV, our observations are in agreement with mature B cells accessing the efferent blood circulation in the efferent, subcapsular area. This understanding of the inverted porcine LN circuitry will allow a more accurate exploration of swine pathogens interactions with the immune cells inside the LN structures. Moreover, the mix between similarities and differences of porcine inverted LN circuitry with mouse and human normal LN shall enable to better apprehend the functions and malfunctions of normal LN from a new perspective.

Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model

“…Total B cells were identified by co-expression of CD79α and Pax5 and plasma cells and plasmablasts by the co-expression of Blimp-1 and IRF4 ( Supplementary Figure 1A ). B cells that did not express these transcription factors were analyzed for Bcl-6, thought to represent porcine germinal center (GC) B cells ( 36 , 37 ). The remaining B cells (CD79α + Pax5 + Blimp-1 - IRF4 - Bcl-6 - ) were a mixture of naïve, memory, and recently activated B cells.…”

Porcine Macrophage Markers and Populations: An Update

“…Compared to mouse and human, swine lymph nodes (LN) have an inverted structure, which is also present in elephants, dolphins, and hippopotamus, with the lymph flowing from the center to the periphery [ 248 , 259 , 260 ].…”

“…Since CD11b expression in porcine lymphoid tissues had been previously associated to DC [ 261 ], it was speculated that these cells might be related to murine CD169 + DC described by Berney et al, which have the capacity to attract and provide antigenic stimulation to lymphocytes [ 262 ]. More recently, Bertho and colleagues have carried out an elegant and detailed analysis of the structure of porcine LN and its different macrophage populations [ 247 , 248 ]. They characterized three macrophage populations: (i) the CD163 − CD169 + macrophages found at the periphery of the B cell follicles and thought to be the counterpart of the murine subcapsular sinus macrophages, which are involved in the translocation of soluble antigens from the afferent lymphatic sinus to the inside of the follicle; (ii) the CD163 + CD169 + macrophages found in the periphery of LN, before the efferent lymphatic vessels, are considered the functional equivalent of the mouse medullary sinus macrophages, which would be involved in the clearance of the lymphatic fluid before its exit to the main blood circulation; (iii) the CD163 + CD169 − macrophages positioned along the medullary cords with a phenotype similar to the murine medullary cord macrophages (MCM), which have a role in the plasma cell terminal maturation [ 263 , 264 ].…”