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Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.

Sacha CR, Vandergrift N, Jeffries TL, McGuire E, Fouda GG, Liebl B, Marshall DJ, Gurley TC, Stiegel L, Whitesides JF, Friedman J, Badiabo A, Foulger A, Yates NL, Tomaras GD, Kepler TB, Liao HX, Haynes BF, Moody MA, Permar SR - Mucosal Immunol (2014)

Bottom Line: To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies.One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified.These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

View Article: PubMed Central - PubMed

Affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.

ABSTRACT
A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

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Related in: MedlinePlus

HIV-1 Env-reactive monoclonal antibodies isolated from colostrum are IgG1 isotypeThe isotype distribution of HIV-1 Env-reactive (left) and nonreactive (right) antibodies isolated from colostrum (top) and blood (bottom) of chronically HIV-1-infected, lactating women is shown by color. The number of antibodies in each population is indicated in the center of each donut.
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Figure 3: HIV-1 Env-reactive monoclonal antibodies isolated from colostrum are IgG1 isotypeThe isotype distribution of HIV-1 Env-reactive (left) and nonreactive (right) antibodies isolated from colostrum (top) and blood (bottom) of chronically HIV-1-infected, lactating women is shown by color. The number of antibodies in each population is indicated in the center of each donut.

Mentions: Nonreactive antibodies produced by blood B cells were primarily IgM isotype (71%), while most nonreactive antibodies in colostrum were IgG1 isotype (55%; Figure 3). A small number of IgA (9%) and IgD (2%) nonreactive antibodies were isolated from blood B cells. Similarly, we found few colostrum B cells producing IgA antibodies (7%), and none were HIV-1 Env-specific. Interestingly, Env-reactive antibodies in colostrum were all IgG1 isotype (100%), consistent with our prior isolation of only IgG1 HIV-1 Env-specific colostrum antibodies.16 In contrast, IgA, IgG1, IgG3, IgD, and IgM Env-reactive antibodies were isolated from blood.


Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.

Sacha CR, Vandergrift N, Jeffries TL, McGuire E, Fouda GG, Liebl B, Marshall DJ, Gurley TC, Stiegel L, Whitesides JF, Friedman J, Badiabo A, Foulger A, Yates NL, Tomaras GD, Kepler TB, Liao HX, Haynes BF, Moody MA, Permar SR - Mucosal Immunol (2014)

HIV-1 Env-reactive monoclonal antibodies isolated from colostrum are IgG1 isotypeThe isotype distribution of HIV-1 Env-reactive (left) and nonreactive (right) antibodies isolated from colostrum (top) and blood (bottom) of chronically HIV-1-infected, lactating women is shown by color. The number of antibodies in each population is indicated in the center of each donut.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4320043&req=5

Figure 3: HIV-1 Env-reactive monoclonal antibodies isolated from colostrum are IgG1 isotypeThe isotype distribution of HIV-1 Env-reactive (left) and nonreactive (right) antibodies isolated from colostrum (top) and blood (bottom) of chronically HIV-1-infected, lactating women is shown by color. The number of antibodies in each population is indicated in the center of each donut.
Mentions: Nonreactive antibodies produced by blood B cells were primarily IgM isotype (71%), while most nonreactive antibodies in colostrum were IgG1 isotype (55%; Figure 3). A small number of IgA (9%) and IgD (2%) nonreactive antibodies were isolated from blood B cells. Similarly, we found few colostrum B cells producing IgA antibodies (7%), and none were HIV-1 Env-specific. Interestingly, Env-reactive antibodies in colostrum were all IgG1 isotype (100%), consistent with our prior isolation of only IgG1 HIV-1 Env-specific colostrum antibodies.16 In contrast, IgA, IgG1, IgG3, IgD, and IgM Env-reactive antibodies were isolated from blood.

Bottom Line: To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies.One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified.These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

View Article: PubMed Central - PubMed

Affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.

ABSTRACT
A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

Show MeSH
Related in: MedlinePlus