Abstract
In the absence of class switch recombination and germinal centers, the mechanisms through which B cells from teleost fish mount extrafollicular immunoglobulin M (IgM) memory responses remains mostly unexplored. In this report, we demonstrate that teleost IgM+ B cells respond to CD40L, a thymus-dependent activation signal, similarly to mammalian B2 cells. However, when stimulated with different types of antigens, fish IgM+ B cells only reach a general activation state in response to antigens cataloged as thymus-independent 1 (TI-1) in mammals, as established through both functional assays and RNA sequencing. Interestingly, fish IgM+ B cells remained completely unresponsive to TI-2 antigens, suggesting that the engagement of innate receptors provided by TI-1 antigens is required for the activation of teleost B cells. Finally, a synergy between CD40L and TI-1 antigens was also demonstrated, further supporting that there is no clear dichotomy between thymus-dependent and TI responses in teleost fish.
Highlights
The classical dogma in mammalian immunology holds that B cell memory can only be achieved within germinal centers (GCs)
Our results show that skin dendritic cells (DCs) significantly upregulated the expression of CD40L in response to LPS or polycytidylic acid (poly I):C, while T cells upregulated the expression of CD40L in response to the T cell mitogen concanavalin A (ConA) (Figure 1A)
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
Summary
The classical dogma in mammalian immunology holds that B cell memory can only be achieved within germinal centers (GCs). Cross-linking of CD40 stimulates the formation of GCs and promotes B cell survival, proliferation and differentiation [2] This TD pathway requires two signals, being “signal 1” that delivered through the B cell receptor (BCR) after recognition of the antigen, and “signal 2” the cognate help from T cells (mainly CD40 cross-linking) [3]. Alternative to this TD response, mammals have additional thymus-independent (TI) pathways to elicit faster antibody responses that are mainly orchestrated by innate B cell subsets, mainly B1 cells or marginal zone (MZ) B cells. TI antigens have been classically classified as type 1 (TI-1) or type 2 (TI-2) depending on whether they can stimulate B cells in CBA/N mice, which have an X-linked immunological defect
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