Ileum Colon Rectum

Mesenteric LN Iliac LN Axillary LN

PBMC Bone marrow Spleen

CD

21

CD27

Supplementary Figure 1

22 0.39

51.626

4.11 0

1.8394

50.2 15.4

16.318.1

73 9.08

5.2712.7

78.2 6.26

4.7110.8

86 4.13

2.727.17

7.89 0.25

0.9690.9

20.5 0.4

0.778.4

29.9 0.99

1.667.5

0

1000

2000

3000

4000

Naïve Resting Tissue Memory

Activated 0 2 12 0 2 12 0 2 12 0 2 12

Cel

ls/µ

l blo

od

0

1000

2000

3000

4000

Naïve Resting Tissue Memory

Activated 0 2 12 0 2 12 0 2 12 0 2 12

Cel

ls/µ

l blo

od

Supplementary Figure 2

Rapid Typical

***

*** ** *

***

***

** * ***

***

*** ***

*

A

B

Week 12 SIV RNA (copies/ml plasma)

103 104 105 106 107 108 1090

500

1000

1500

2000

2500Week 12

P < 0.0001 r = -0.7

103 104 105 106 107 108 1090

100

200

300

400

500

600

700Week 2

P = 0.03 r = -0.4

Cel

ls/µ

l blo

od

Supplementary Figure 3

IgG IgM SIV gp130

Unstimulated

Mitogen-Stimulated

Mitogen-Stimulated + α-PD-1

2-fold dilutions 2-fold dilutions 2-fold dilutions

A B

D

PD-L1

% o

f max

0 5

10 15 20 25 30 35 40 45

Ann

exin

+ m

BA

ct c

ells

(%)

1 2 3

Huh 7.5 Huh 7.5-PD-L1

C

FasL -

Ann

exin

+ m

BA

ct c

ells

(%)

01020304050607080

FasL+ α-PD-1

*** **

Supplementary Figure 1. Representative flow cytometric dot plots showing distribution

of B cell subsets in tissues of an uninfected rhesus macaque. Cells were gated on CD20+

cells. Numbers represent proportion of each subset as a percentage of CD20+ cells.

Supplementary Figure 2. (A). Absolute counts of B cell subsets in rapid progressors (n=

13) and typical progressors (n = 39) pre- (Week 0) and post- (Weeks 2 and 12) SIV

infection. Each data point represents an individual animal, and horizontal lines represent

medians. (B) Correlations between set-point viral load and absolute numbers of mBAct

cells at 2 or 12 weeks post SIV infection; filled and open symbols represent rapid and

typical progressors, respectively. *, P < 0.05; **, P < 0.01; ***, P< 0.001.

Supplementary Figure 3. (A) Representative FACS histogram plots demonstrating the

expression of PD-L1 on Huh-7.5 (closed) and Huh-7.5.PD-L1 (open) cells. (B) Summary

of Annexin-V expression on mBAct cells of SIV- rhesus macaques (n = 3) following

culture with Huh 7.5 or Huh 7.5-PD-L1 cells. (C) PBMC were purified from 9 SIV-

infected animals and cultured for 24hrs in medium only, in the presence of rFasL or in

the presence of rFasL + anti-PD-1 blocking Ab. Following culture, cells were stained for

Annexin-V on different B cell subsets. (D) Representative ELISpots for total IgM, total

IgG and SIV Env gp130-specific IgG under 3 conditions: unstimulated (medium only),

stimulated (mitogens only) and stimulated + anti-PD-1 blocking Ab. Each spot represents

an individual Ab-secreting cell. *, P < 0.05; **, P < 0.01; ***, P< 0.001.

 

Supplementary Table 1. Rapid progressor non-SIV infections

Campylobacter spp-1, Shigella-2, Trichomonas-3, whipworms-4, enteropathogenic E.coli-5, diarrhea-6, trauma-7, abscess-8, eye problems-9, Candida-10, pain-11, Giardia-12, anemia-13, unknown-14

Animal ID Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 RP 1 1 3 6 6 RP 2 1, 4 1, 4, 13 RP 3 2 1, 2 1, 6 6, 13 RP 4 6 6, 13 1, 11 RP 5 RP 6 6 6 RP 7 1, 4, 6 8 RP 8 1, 3, 6 RP 9 1, 5 5, 6 6 6 RP 10 3,4 1 RP 11 2 6 6 RP 12 1, 5 1 5 5, 6 RP 13 1, 6, 12 1, 6, 12

Supplementary Table 2. Typical progressor non-SIV infections

Animal ID Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 TP 1 TP 2 1 TP 3 TP 4 TP 5 TP 6 TP 7 TP 8 TP 9 TP 10 TP 11 3 TP 12 3 6 6 6 TP 13 3 3, 6 4 TP 14 TP 15 TP 16 6 1P 17 TP 18 7 TP 19 1 TP 20 TP 21 1 TP 22 2, 3 TP 23 TP 24 3 3 2 TP 25 5, 6 6 1, 6, 10, 11 TP 26 7, 11 7, 11 TP 27 TP 28 12 TP 29 TP 30 2, 3 2, 3 TP 31 TP 32 TP 33 6 5, 6 6 TP 34 TP 35 6 6 TP 36 1 TP 37 TP 38 2 6 1 TP 39

Campylobacter spp-1, Shigella-2, Trichomonas-3, whipworms-4, enteropathogenic E.coli-5, diarrhea-6,

trauma-7, abscess-8, eye problems-9, Candida-10, pain-11, Giardia-12, anemia-13, unknown-14

Supplementary Table 3. Statistical tests

Figure Statistical test used 1B t-test 2C Wilcoxon signed rank test 2D Paired t-test 3A t-test 3B Pearson’s product moment correlation

3C (box plots) t-test (Wk2) and Wilcoxon rank sum test (Wk12) 3D (box plots) Wilcoxon rank sum test 3E (box plots) t-test (Wk2) and Wilcoxon rank sum test (Wk12)

3C, D and E (Correlations) Pearson’s product moment correlation 4C Wilcoxon signed rank test 5C Paired t-test 6B Paired t-test 6D t–test (IgM) and Wilcoxon rank-sum test (IgG)

Supplementary Figure 2A Paired t-test Supplementary Figure 2B Pearson’s product moment correlation Supplementary Figure 3C Paired t-test