Common variable immunodeficiency (CVID) and selective IgG1 deficiency are primary 55 immunodeficiencies characterized by defective antibody production leading to recurrent 56 infections of the respiratory tract 1-3. Recent studies have identified CD19 and CD81 biallelic 57 mutations as underlying CVID in humans. On mature B cells, CD19 functions in a complex 58 with CD21, CD81, and CD225 and acts synergistically with the B cell antigen receptor to 59 induce activation and maturation of the activated B cells into the memory compartment 4. 60 Only five patients with bi-allelic deleterious mutations in CD19 have been described to date 5-61 7. Despite variability in CD19 expression, these patients display a remarkable similar 62 phenotype characterized by moderately severe hypogammaglobulinemia, impaired antibody 63 responses upon vaccination and impaired memory B cell formation. We report on two 64 additional patients with CD19 deficiency from two different families. 65 Out of 400 patients from the French national DEFI cohort with primary 66 hypogammaglobulinemia, 18 had CD19+ cells< 1% but a percentage of T, NK and CD19 B 67 cells that didn’t add up to 100%. Double CD19/CD20 staining performed in these 18 patients 68 demonstrated a CD19 defect in two patients (Figure E1). 69 Patient A, a girl of Kurdish descent was referred at 11 years of age with pneumococcal 70 meningitis. She also had a history of recurrent upper respiratory tract infections and giardiasis 71 starting in early childhood. She was found to have hypogammaglobulinemia and impaired 72 antibody response to vaccination (Table E1). Patient B, a girl of Moroccan descent and the 73 second child of consanguineous parents was first referred at 13 years of age with failure to 74 thrive. Urinalysis revealed microscopic hematuria and proteinuria without renal failure. Tests 75 for antinuclear antibodies were positive (titer= 1/640) in the absence of anti-DNA and anti-76 ENA antibodies. The complement levels were normal. At 27 years of age, she had surgery for 77 chronic sinusitis and at 29 years of age she developed pneumococcal pneumonia. She was 78