Shark immunity bites back: affinity maturation and memory response in the nurse shark, <i>Ginglymostoma cirratum</i>

TLDR

Cartilaginous fish, the earliest vertebrates with a complete adaptive immune repertoire, were known to mount IgM responses but lacked clear evidence for memory, affinity maturation, or IgNAR involvement, and their B‑cell lineages appear fixed to a single isotype due to absent isotype switching. The study proposes that sharks possess distinct B‑cell lineages, each committed to a single isotype. The data demonstrate that nurse sharks generate both IgM and IgNAR responses, with memory elicitable for each, and reveal that pentameric IgM serves as a high‑avidity, low‑affinity first‑line defense while monomeric IgM and IgNAR mediate specific antigen‑driven immunity, suggesting separate B‑cell lineages for each IgM form.

Abstract

The cartilaginous fish are the oldest phylogenetic group in which all of the molecular components of the adaptive immune system have been found. Although early studies clearly showed that sharks could produce an IgM-based response following immunization, evidence for memory, affinity maturation and roles for the other isotypes (notably IgNAR) in this group remained inconclusive. The data presented here illustrate that the nurse shark (Ginglymostoma cirratum) is able to produce not only an IgM response, but we also show for the first time a highly antigen-specific IgNAR response. Additionally, under appropriate conditions, a memory response for both isotypes can be elicited. Analysis of the response shows differential expression of pentameric and monomeric IgM. Pentameric IgM provides the 'first line of defense' through high-avidity, low-affinity interaction with antigen. In contrast, monomeric IgM and IgNAR seem responsible for the specific, antigen-driven response. We propose the presence of distinct lineages of B cells in sharks. As there is no conventional isotype switching, each lineage seems pre-determined to express a single isotype (IgM versus IgNAR). However, our data suggest that there may also be specific lineages for the different forms (pentameric versus monomeric) of the IgM isotype.