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. 2019 Oct 2;10:2324.
doi: 10.3389/fimmu.2019.02324. eCollection 2019.

Long-Lived Plasma Cells Secrete High-Affinity Antibodies Responding to a T-Dependent Immunization in a Teleost Fish

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Free PMC article

Long-Lived Plasma Cells Secrete High-Affinity Antibodies Responding to a T-Dependent Immunization in a Teleost Fish

Liting Wu et al. Front Immunol. .
Free PMC article

Abstract

The recent discovery of long-lived plasma cells (LLPCs) in mammals, which provide a constant expression of specific high-affinity antibodies that mediate humoral memory, has caused a dramatic paradigm shift in the study of immunity and vaccine development. In teleost fish, there are few studies regarding the association between LLPCs and antibody production, and the affinity of the antibodies secreted by the LLPCs is poorly understood. In the present study, channel catfish (Ictalurus punctatus) were immunized with trinitrophenylated-keyhole limpet hemocyanin (TNP-KLH) to examine TNP-specific antibody titers, affinities, antibody-secreting cell (ASC) dynamic changes, and especially the affinity of secreted antibodies by LLPCs post-immunization. We demonstrated that TNP-specific LLPCs were generated starting at week 4 post-immunization, achieved a maximal number at week 8, and maintained a comparable level throughout the 18-week post-immunization period, which was correlated with the dynamics of serum antibody titers and affinity maturation in the response. The LLPCs appeared to mostly reside within, or migrate to, the anterior kidney (bone marrow-like tissue in mammals), but a small portion was also located in the spleen and peripheral blood. The antibodies produced by the LLPCs possessed high affinities, indicating that the generation and development of LLPCs were driven by affinity selection in teleosts. Collectively, the results of this study provide insights toward the evolutionary understanding of the affinity-dependent mechanism of LLPC generation and development.

Keywords: Ictalurus punctatus; affinity; affinity-driven selection; anterior kidney; long-lived plasma cells.

Figures

Figure 1
Figure 1
Anti-TNP antibody titers and affinities induced by trinitrophenylated-keyhole limpet hemocyanin (TNP-KLH) (n = 5). The dynamics of anti-TNP antibody titers were detected by standard antibody titration ELISA (A). The T1/T8 ratio was used to present the dynamic of antibody maturation (B), and affinity partitioning ELISA (C) was used to detect the differential dynamics of antibody subpopulations at weeks 2, 6, and 18 post-immunization. Week 0 was bled prior to immunization, and PBS was immunized as the control. Data represent the mean ± standard deviation (SD) of five individual fish at each time point and are representative of three independent experiments.
Figure 2
Figure 2
ELISPOTs of anti-TNP-specific antibody-secreting cells (ASCs) (in vivo) in immune tissues. The ELISPOTs of the in vivo ASC response within peripheral blood (PBL), spleen (SPL), and anterior kidney (AK) were shown from an individual fish immunized with TNP-KLH by 1 × 106 leukocytes per well (A). The average number of ASCs per 106 leukocytes (B,D) and the total number of ASCs in each tissue (C,E) were detected at weeks 0, 2, 4, 6, 8, 10, 14, and 18 post-immunization (n = 5) with TNP-KLH (B,C) and PBS (D,E). Data represent the mean ± SD of five individual fish at each time point and are representative of three independent experiments.
Figure 3
Figure 3
Kinetics of TNP-specific plasma (HU-insensitive, in vitro D7). The average number per 106 leukocytes (A,C) and the total number in each tissue (B,D) detected in peripheral blood, spleen, and anterior kidney (n = 5) immunized with TNP-KLH (A,B) and PBS (C,D). Data represent the mean ± SD of five individual fish at each time point and are representative of three independent experiments.
Figure 4
Figure 4
Kinetics of TNP-specific LLPCs (HU-insensitive, in vitro D15). The average number per 106 leukocytes (A,C) and the total number in each tissue (B,D) detected in peripheral blood, spleen, and anterior kidney (n = 5) immunized with TNP-KLH (A,B) and PBS (C,D). Data represent the mean ± SD of five individual fish at each time point time point and are representative of three independent experiments.
Figure 5
Figure 5
Kinetics of TNP-specific antibody titers and affinities secreted by LLPCs. The sample of detection was from the supernatant of HU-resistant plasma cells cultured in vitro for 15 days. The antibody titer (A) and affinity (B) shown are the average of five fish (n = 5). The PBS-immunized group was used as the control. Error bars represent standard deviation of the mean.
Figure 6
Figure 6
LLPCs (in vitro D15) have a strong capability to secrete antibodies compared to that of other ASCs (ex vivo and in vitro D7). ELISPOTs of TNP-specific ASCs from different immune tissues of vaccinated channel catfish 8 weeks post-immunization (2 × 106 leukocytes per well) (A). The average ELISPOT size of AK LLPCs relative to ASCs (ex vivo). Statistical difference was evaluated by t-test, and ***p < 0.001 (B).
Figure 7
Figure 7
A proposed model of tissue distribution and migration of LLPCs from teleosts. Anterior kidney is the bone marrow-like tissue posing the major site of B lymphocyte development where B cell progenitors and naive B cells arise. They migrate to peripheral tissue via the blood. When these B cells encounter antigen, they mature into plasmablasts or PCs in either the anterior kidney or spleen. Plasmablasts or PCs differentiate within the spleen and anterior kidney, but home to the anterior kidney, wherein PCs from all tissues compete for long-term maintenance within the survival niches in the anterior kidney.

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