Identification of the First Teleost CD5 Molecule: Additional Evidence on Phenotypical and Functional Similarities between Fish IgM+ B Cells and Mammalian B1 Cells

Abstract

Despite teleost fish being the first animal group in which all elements of adaptive immunity are present, the lack of follicular structures, as well as the fact that systemic Ab responses rely exclusively on unswitched low-affinity IgM responses, strongly suggests that fish B cell responses resemble mammalian B1 cell responses rather than those of B2 cells. In line with this hypothesis, in the current study, we have identified a homolog of CD5 in teleost fish. This pan-T marker belonging to the scavenger receptor cysteine-rich family of receptors is commonly used in mammals to distinguish a subset of B1 cells. Subsequently, we have demonstrated that a very high percentage of teleost IgM B cells express this marker, in contrast to the limited population of CD5-expressing B1 cells found in most mammals. Furthermore, we demonstrate that fish IgM B cells share classical phenotypic features of mammalian B1 cells such as large size, high complexity, high surface IgM, and low surface IgD expression, regardless of CD5 expression. Additionally, fish IgM B cells, unlike murine B2 cells, also displayed extended survival in cell culture and did not proliferate after BCR engagement. Altogether, our results demonstrate that although fish are evolutionarily the first group in which all the elements of acquired immunity are present, in the absence of follicular structures, most teleost IgM B cells have retained phenotypical and functional characteristics of mammalian B1 cells.

Rainbow Trout IgM+ B Cells Preferentially Respond to Thymus-Independent Antigens but Are Activated by CD40L

“…In conclusion, we have demonstrated that teleost fish preferentially respond to TI antigens over TD antigens, in correlation with the many similarities found between fish IgM + B cells and mammalian B1 cells (60). Despite this, fish IgM + B cells responded to TD antigens activating the transcription of several genes related to immune processes, many of which lead to the activation of the NF-κB pathway.…”

“…In teleost fish, the fact that no cognate GCs are ever organized and there is no CSR seem to account for the low affinity maturation of antibodies during the primary and secondary immune responses observed in these species (56,57). Furthermore, a substantial amount of evidence has been gathered by different authors in recent years pointing to a phenotypic and functional resemblance between fish IgM + B cells and mammalian B1 cells (58)(59)(60)(61). In this context, under the mammalian paradigm that long-lived memory responses are only achieved through TD class-switched responses mounted within GCs, it would seem plausible to predict that teleost fish are not able to mount long-lived B cell memory responses.…”

Regulation of IgM+ B Cell Activities by Rainbow Trout APRIL Reveals Specific Effects of This Cytokine in Lower Vertebrates

“…As a consequence, fish B cells are one main cell types implicated in the early response to inflammation ( 25 , 46 ). Furthermore, fish B cells have a similar surface IgM/IgD ratio, size, and complexity than mammalian B1 cells ( 47 ). In addition, unlike mammalian B2 cells and similar to B1 cells, fish IgM + B cells are incapable of proliferating upon BCR cross-linking ( 47 ).…”

“…Furthermore, fish B cells have a similar surface IgM/IgD ratio, size, and complexity than mammalian B1 cells ( 47 ). In addition, unlike mammalian B2 cells and similar to B1 cells, fish IgM + B cells are incapable of proliferating upon BCR cross-linking ( 47 ). In this context, it seems interesting to establish how cytokines of the TNF ligand superfamily affect fish B cells, taking into account that B2 and B1 cells seem to respond differently in mammals to these cytokines ( 35 , 41 ).…”

“…Interestingly, these effects appeared exclusively on IgM + B cells, suggesting that IgT + B cells are not regulated by APRIL or are regulated in a different way. Taking into account that teleost IgM + B cells share many functional and phenotypical characteristics of mammalian B1 cells which mediate TI responses in mammals ( 47 ); and knowing that teleost fish do not produce GCs and therefore respond to antigens extrafollicularly, without having a specific site in which they can interact with T cells ( 54 ); it seems plausible to hypothesize that APRIL preferentially regulates TI processes both in mammals and fish through the regulation of early IgM responses.…”